As a supplement to oral rehydration and dietarymeasures, symptomatic treatment of acute
diarrhoea in children.
The degree of rehydration by oral or intravenous rehydration solution must be adapted to the
intensity of the diarrhoea and the child’s age and specific circumstances (associated illnesses,
etc.).

Oral use.
Hidrasec 30 mg is indicated in children weighing more than or equal to 13 kg.
Posology
The standard daily dosage is established according to body weight on the basis of 1.5 mg/kg
per dose, with a loading dose, then three doses spread throughout the day.
In practice:
Number of pouches per dose based on the child's body weight:
• For a child weighing 13-27 kg: 1 x 30 mg pouch, 3 times daily
• For a child weighing more than 27 kg: 2 x 30 mg pouches, 3 times daily.

Method of administration
The powder can be poured either onto food or into a glass of water or feeding bottle, stirring
well and ensuring that the whole of the mixture is swallowed immediately.
Day 1: Loading dose, then 3 doses spread throughout the day. On the following days: 3 doses spread throughout the day.
Treatment must be continued until the return of two formed stools, without exceeding 7 days.
Specific populations:
No studies have been conducted in children with hepatic or renal insufficiency (see section
4.4).

Treatment with Hidrasec is merely an adjuvant therapy in addition to oral rehydration and does
not in any way substitute it. Rehydration must be systematic in infants/children with acute
diarrhoea to prevent or treat dehydration and must be adapted in such a way as to compensate
for fluid and electrolyte losses.
Treatment of acute diarrhoea in children is primarily based on correcting fluid and electrolyte
losses, by using oral rehydration solutions and re-establishing feeding patterns as soon as
possible, depending on the child’s age and dietary habits prior to diarrhoea.
In cases of severe or prolonged diarrhoea, significant vomiting or refusal of food, intravenous
rehydration must be envisaged.
The presence of blood or pus in the stools with fever can be a sign of diarrhoea with invasive
germs or indicate the presence of other ongoing diseases. In the case of infectious diarrhoea
with clinical manifestations suggesting an invasive phenomenon, use antibacterial agents with
good systemic diffusion. Racecadotril has not been evaluated in antibiotic-associated
diarrhoea. Hence, racecadotril must not be
used in these cases.
Due to potentially reduced bioavailability, racecadotril must not be administered in cases of
prolonged or uncontrollable vomiting.
This medicinal product contains sucrose. Its use is not recommended in patients with fructose
intolerance, glucose-galactosemalabsorption or sucrase/isomaltase deficiency.
This medicinal product contains about 2.899 g sucrose per pouch.
If the quantity of sucrose (source of glucose and fructose) in the daily dose of this medicine
exceeds 5 g per day, this must be taken into account in the daily sugar allowance of patients
on a low-sugar diet or with diabetes.
In cases of renal or hepatic insufficiency, HIDRASEC must not be administered due to the
absence of data.
Skin reactions have been reported with the use of this medicinal product. In most cases, these
reactions are mild and do not require any treatment. However, in certain situations, these
reactions may be severe and be life-threatening; the link with taking racecadotril cannot be
entirely excluded. If severe skin reactions appear, treatment with racecadotril must be
discontinued immediately.
Cases of hypersensitivity and angioedema have been reported in patients treated with
racecadotril. These events can occur at any time during treatment.
Angioedema of the face, extremities, lips, mucous membranes may occur.
When angioedema is associated with obstruction of the upper respiratory tract, such as the
tongue, glottis and / or larynx, emergency treatment should be given immediately. Racecadotril should be discontinued and the patient should be closely monitored with
initiation of appropriate follow-up until symptoms are completely and permanently resolved.
Patients with a history of angioedema not associated with racecadotril therapy may have an
increased risk of developing angioedema.
Concomitant use of racecadotril and ACE inhibitors may increase the risk of angioedema (see
section 4.5). Therefore, a rigorous benefit-risk assessment is required before initiating
treatment with racecadotril in patients on ACE inhibitors.

Interaction of racecadotril with angiotensin-converting enzyme (ACE) inhibitors.
Risk of intensifying the undesirable effects of the angioneurotic oedema type (angioedema).

Contraindicated association:
· in case of a history of angioedema when taking an ACE inhibitor.
Association not advised:
· in the absence of a history of angioedemawhen taking an ACE inhibitor.
In humans, concomitant intake of racecadotril with loperamide or nifuroxazide does not alter
the kinetics of racecadotril.

Pregnancy
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive
toxicity. Clinical data on the use of racecadotril during pregnancy are very limited. As a
precaution, it is therefore preferable to avoid the use of HIDRASEC during pregnancy,
regardless of the term.
Breastfeeding
In the absence of data on passage into milk and on account of its pharmacological properties
and the immaturity of the neonatal digestive tract, HIDRASEC should not be administered
during breastfeeding.
Fertility
No effect on fertility has been observed during fertility studies conducted in male and female
rats.

Racecadotril has no or negligible influence on the ability to drive and use machines.

Clinical studies conducted on acute diarrhoea have provided safety-in-use data in 860 infants
and children treated with racecadotril and 441 treated with placebo.
The adverse reactions listed below have been observed more frequently with racecadotril than
with placebo during clinical trials, or have been reported during the post-marketing phase.
The frequency of adverse reactions has been defined according to the following convention:
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), not known (cannot be estimated from the
available data).
Skin and subcutaneous tissue disorders
Uncommon: rash, erythema
Not known: urticaria, angioedema (oedema of the tongue, face, lips or eyelids), erythema
multiforme, erythema nodosum, papular rash, pruritus, prurigo. 

To report any side effect(s):

National Pharmacovigilance Center (NPC)
Fax: +966-1-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail:npc.drug@sfda.gov.sa
Website:www.sfda.gov.sa/npc

In the cases of overdose reported, patients did not present with any undesirable effects.

Pharmacotherapeutic group: INTESTINAL ANTISECRETORYANTIDIARRHOEAL.
ATC code: A07XA04. (A: digestive systemand metabolism).
Racecadotril is a prodrug that needs to be hydrolysed to its active metabolite thiorphan, which
is an inhibitor of enkephalinase, a cell membrane enzyme present in various tissues, including
the intestinal epithelium.
This enzyme contributes to the hydrolysis of exogenous and endogenous peptides, such as
enkephalins.
Racecadotril thus protects enkephalins from enzymatic degradation, thereby prolonging their
action at enkephalinergic synapses in the small intestine and thus reducing hypersecretion.
Racecadotril is a pure intestinal antisecretory agent. It decreases intestinal hypersecretion of
water and electrolytes induced by cholera toxin or inflammation, with no effect on basal
secretion. It exerts antidiarrhoeal activity without altering the intestinal transit time.
In two clinical studies performed in children, racecadotril reduced stool weight within the first
48 hours by 40% and 46%, respectively.
A significant reduction in the duration of diarrhoea and the need for rehydration was also
observed.
A meta-analysis based on individual data (9 randomised clinical trials, racecadotril versus
placebo, plus oral rehydration solution) collected individual data from 1,384 boys and girls
with acute diarrhoea of varying severity, treated in an outpatient or hospitalised setting.
The mean age was 12 months (interquartile range: 6-39 months). A total of 714 patients were less than 1 year old and 670 patients were more than 1 year old.
The mean
weight ranged from 7.4 kg to 12.2 kg, depending on the study. The overall mean duration of
diarrhoea after enrolment was 2.81 days in the placebo group and 1.75 days for racecadotril.
In oral use, the activity of racecadotril remains peripheral without any effect on the central
nervous system.
A randomised, crossover clinical study has shown that 100 mg racecadotril at the therapeutic
dose (one capsule) or at a higher dose (4 capsules) does not induce QT/QTc prolongation in
56 healthy adult volunteers (unlike the effect observed with moxifloxacin, used as a positive
control).

Absorption:
After oral administration, racecadotril is rapidly absorbed. The activity on plasma
enkephalinase appears from the 30th minute onwards.
The bioavailability of racecadotril is not altered by food, but the activity peak is delayed by
about one and a half hours.
Distribution:
After oral administration of 14C-labelled racecadotril in healthy volunteers, the concentration
of racecadotril was about 200 times higher in the plasma than in blood cells and about 3 times
higher in the plasma than in the total blood volume. Racecadotril does not significantly bind
to blood cells.
In plasma, the mean apparent volume of distribution of 66.4 kg demonstrates moderate
distribution of 14C in other tissues.
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 are not altered during repeat-dose
administration or in the elderly.
The intensity and duration of action of racecadotril are related to the administered dose. The
peak concentration is about 2 hours 30 min., corresponding to 90% inhibition of enzymatic
activity for the administered dose of 1.5 mg/kg.
For a 100 mg dose, the duration of plasma enkephalinase activity is about 8 hours.
Metabolism:
The biological half-life of racecadotril, as determined by plasma enkephalinase inhibition, is 3
hours.
Racecadotril is rapidly hydrolysed to thiorphan (RS)-N-(1-oxo-2-(mercaptomethyl)-3-
phenylpropyl) glycine, its active metabolite, which is itself transformed into inactive
metabolites S-methylthiorphan sulphoxide, S- methylthiorphan, 2-methanesulfinylmethyl
propionic acid and 2-methylsulfanylmethyl propionic acid, which were all formed at greater
than 10% systemic exposure to the parent compound.
Other minor metabolites have also been detected and quantified in urine and faecal matter.
Repeated administration of racecadotril does not induce accumulation within the body.
In vitro data show that racecadotril/thiorphan and its four major inactive metabolites have no
significant action as inhibitors of the cytochrome CYP isoforms 3A4, 2D6, 2C9, 1A2 and
2C19.
In vitro data show that racecadotril/thiorphan and its four major inactive metabolites have no significant action as inducers of cytochrome CYP isoforms (family 3A, 2A6, 2B6, 2C9/2C19,
family 1A, 2E1) and enzymes that bind to glucuronyl transferase.
Racecadotril does not alter the protein binding of highly protein-bound products, such as
tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.
In patients with hepatic insufficiency (cirrhosis, Child-Pugh B), the kinetic profile of the
metabolite shows the same Tmax and T½ and lower Cmax (-65%) and areas under the curve
(-29%), compared to healthy subjects.
In patients with severe renal insufficiency (creatinine clearance between 11 and 39 mL/min),
the kinetic profile of the metabolite shows a lower Cmax (-49%) and larger areas under the
curve (15%) and T½, compared to healthy volunteers (creatinine clearance > 70 mL/min).
In the paediatric population, the pharmacodynamic results are similar to those of the adult
population, with Cmax reached 2 hours 30 minutes after administration. There is no
accumulation after repeated doses every 8 hours for 7 days.
Excretion:
Racecadotril is eliminated via its active and inactive metabolites. Elimination takes place
mainly via the kidneys (81.4%) and, to a lesser degree, via the faeces (about 8%). Excretion
via the lungs is not significant (less than 1% of the dose).

4-week chronic toxicity studies performed in monkeys and dogs, useful for the assessment of
the duration of treatment in humans, have demonstrated no effect at dosages up to 1250
mg/kg/day and 200 mg/kg, corresponding to safety margins of 625 and 62 (compared to
humans), respectively.
Racecadotril has not been shown to be immunotoxic in mice treated for 1 month.
A longer duration of exposure (1 year) in monkeys showed generalised infections and reduced
antibody responses to vaccinations (at a dose of 500mg/kg/day) and no
infection/immunosuppression at
120 mg/kg/day.
Similarly, in dogs treated at a dose of 200 mg/kg/day for 26 weeks, some infectious/immune
reactions were detected. Their clinical significance is unknown: see paragraph 4.8.
No mutagenic or clastogenic effect of racecadotril was detected during standard tests in vivo
and in vitro. No carcinogenicity tests have been conducted, as treatment is short-term.
Reproductive toxicity and development studies (pre-embryonic development and fertility,
prenatal and postnatal development, embryofoetal development studies) revealed no particular
effect of racecadotril.
A toxicity study conducted in juvenile rats showed no significant effect due to racecadotril at
doses up to 160 mg/kg/day, corresponding to a dose 35 times higher than the recommended
paediatric dose (e.g.
4.5 mg/kg/day).
Despite the immaturity of renal function in children under 1 year old, higher exposure levels
are not expected in this group.
Other preclinical effects (such as severe, probably aplastic anaemia, increased diuresis,
ketonuria, diarrhoea) were observed only at much higher exposures compared to the
maximum human dose. Their clinical significance is not known.
Other safety pharmacology studies revealed no harmful effects on the central nervous system,
the cardiovascular system and respiratory functions.
In animals, racecadotril potentiates the effect of butylhyoscine on intestinal transit and the
anticonvulsant effect of phenytoin.

Sucrose

anhydrous colloidal silica

30% polyacrylate dispersion

 apricot flavouring (vanillin,
gamma undecalactone, gamma nonalactone, allyl caproate, lemon, neroli, orange, gum arabic,
maltodextrin, sorbitol).

Not applicable.

This medicinal product does not require any special storage conditions.

3 g powder in pouches (PE/paper/aluminium); box of 16.

No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.