a. Therapeutic indications
Hidrasec is indicated in the symptomatic treatment of acute diarrhoea in adults in addition to dietary
measures.

Posology
Oral administration.
For adults only.
Adults:
Day 1: a starting dose, at any time, then, depending on the time of the first dose, up to a maximum of three
capsules in divided daily doses (including the first dose). Medication should preferably be administered at the
beginning of the three main meals.
Subsequent days: three capsules in divided daily doses, preferably at the beginning of the three main meals.
Not more than three capsules must be taken per day.
The treatment is to be continued until there is a return to two consecutive solid stools. Never take for longer than
7 days.
Specific populations:
Paediatric population:
Hidrasec 100 mg, capsule, must not be administered to infants and children.
Other pharmaceutical forms of Hidrasec are suitable for administration to the paediatric population.
Elderly population:

Dose adjustment does not appear justified in elderly subjects (see section 5.2).

Hidrasec treatment does not dispense with rehydration, if required.
Racecadotril must not be used if the signs of acute dysenteric syndrome are present such as bloody stools or
fever.
Racecadotril has not been assessed and must not be used during antibiotic-related diarrhoea.
There is an inadequate amount of data on chronic diarrhoea with this medicinal product.
Bioavailability may be reduced in patients with prolonged vomiting.
Hepatic and renal impairment:
The data are limited in patients presenting hepatic or renal impairment., Caution should, therefore, be exercised
when treating these patients (see section 5.2).
Excipients:
Patients presenting galactose intolerance, total lactase deficiency or glucose and galactose malabsorption
syndrome (rare hereditary diseases) must not take this medicinal product.
Hypersensitivity:
Skin reactions have been reported with the use of this medicinal product. In the majority of cases, these reactions
are mild and do not require treatment. In some situations, however, these reactions can be severe and potentially
life-threatening. The link associated with the administration of racecadotril cannot be entirely ruled out. If
serious skin reactions appear, racecadotril treatment must be discontinued immediately.
Cases of hypersensitivity and Quincke’s oedema have been reported in patients receiving racecadotril. These
events may occur at any time during treatment.
Angioedema of the face, extremities, lips and mucosa may appear.
Emergency treatment should be administered rapidly if the angioedema is associated with an upper respiratory
tract obstruction, e.g. in the region of the tongue, glottis, and/or larynx.
Racecadotril must be discontinued and the patient placed under close, appropriate medical supervision. This
should be continued until symptoms permanently disappear in the long-term. Racecadotril must not be
reintroduced.

Bradykinin-mediated angioedema:

Racecadotril or certain therapeutic classes are likely to trigger an angioedema-type vascular reaction of the
face and neck, resulting from inhibition of bradykinin degradation (see section 4.8).
Angioedema can sometimes have fatal consequences due to obstruction of the airways. It can occur
independently of the concomitant administration of these medicinal products in cases where the patient has
had previous exposure to one of the two protagonists. The history of onset of this effect should be investigated
and the need for this type of combination therapy assessed.

Concomitant administration of racecadotril with certain medicinal products increasing bradykinin levels,
especially angiotensin converting enzyme (ACE) inhibitors (e.g. perindopril and ramipril), increases the risk
of bradykinin-mediated angioedema (see section 4.5)
A rigorous assessment of the benefit/risk ratio is therefore required before introducing racecadotril treatment
to patients receiving angiotensin converting enzyme inhibitors (see section 4.5).

Association to be avoided:
Medicinal products, bradykinin and angioedema
Certain medicinal products or therapeutic classes are likely to trigger an angioedema-type vascular
reaction of the face and neck resulting from inhibition of bradykinin degradation. ACE inhibitors (e.g.
perindopril and ramipril) are most frequently involved and, to less of an extent, angiotensin II
antagonists (e.g.: candesartan, irbesartan), so-called mTORi (mammalian target of rapamaycin
inhibitor) immunosuppressants, gliptin class antidiabetic agents, racecadotril, estramustine, sacubitril
and alteplase recombinant.
Angioedema can sometimes have fatal consequences due to obstruction of the airways. It can occur
independently of the concomitant administration of these medicinal products in cases where the patient has
had previous exposure to one of the two protagonists. The history of onset of this effect should be investigated
and the need for this type of combination therapy assessed.
Association to be avoided (see also section 4.4)
+ Other medicinal products posing a risk of bradykinin-mediated angioedema (see the Medicinal
products, bradykinin and angioedema section).
Others
The concomitant administration of racecadotril with loperamide or nifuroxazide does not modify the
kinetic profile of racecadotril.

Pregnancy
Animal studies have not revealed any direct or indirect harmful toxic effect on reproduction. Clinical data on the
use of racecadotril during pregnancy are very sparse. Therefore, as a precautionary measure, Hidrasec should be
avoided during pregnancy, regardless of trimester.
Breast-feeding
Given the lack of data regarding the diffusion of racecadotril into human milk, and because of its
pharmacological properties and the immaturity of the digestive tract in newborns, Hidrasec should not be
administered during breast-feeding.
Fertility
No effect on fertility has been observed during fertility studies conducted in male and female rats.

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

Clinical trials focusing on acute diarrhoea have provided data from 2,193 adults treated with racecadotril and
282 receiving placebo.
The adverse drug reactions listed below have been observed more frequently with racecadotril than with
placebo during clinical trials or were reported during the marketing period.
The adverse drug reactions are listed according to the main MedDRA system organ classes. Within each system
organ class, the adverse reactions are listed according to frequency. Within each frequency group, the adverse
reactions are listed in decreasing order of seriousness. 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), frequency not known (cannot be estimated on the
basis of the data available).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked
to report any suspected adverse reactions via:
To report any side effect(s):
• National Pharmacovigilance Center (NPC)
• Fax: +966-1-205-7662
• Call NPC: 1999
• E-mail: npc.drug@sfda.gov.sa
• Website: https://ade.sfda.gov.sa

None of the patients presented any adverse reactions in the overdose cases reported to date.

Pharmacotherapeutic class: OTHER ANTIDIARRHETIC (INTESTINAL ANTI-SECRETORY
MEDICATION).
ATC code: A07XA04. (A: Digestive system and metabolism).
Racecadotril is a prodrug which must be hydrolysed into its active metabolite, thiorphan, which is an
inhibitor of enkephalinase, an enzyme of the cellular membrane, present in different tissues including
the intestinal epithelium.
This enzyme contributes to the hydrolysis of exogenic and endogenic peptides, such as enkephalins.
Racecadotril therefore protects enkephalins against enzymatic degradation, thus prolonging their action on the
enkephalinergic synapses of the small intestine and reducing hypersecretion.
Racecadotril is a pure intestinal anti-secretory substance. It reduces the intestinal hypersecretion of water
and electrolytes induced by the cholera toxin or inflammation, without impacting basal secretion. It acts as
an anti-diarrhoeal agent without altering intestinal transit time.
Racecadotril does not cause abdominal flatulence. During clinical trials, secondary constipation was observed at
the same frequency in the racecadotril and placebo groups.
Only peripheral activity is observed following oral administration. There is no effect on the central nervous
system.
A randomised, cross-over clinical study has shown that racecadotril 100 mg administered at the therapeutic
dose (1 capsule) or a higher dose (4 capsules) did not prolong the QT/QTc interval in 56 healthy adult
volunteers (unlike the effect observed with moxifloxacin, used as a positive control).

Absorption:
Racecadotril is rapidly absorbed following oral administration. Plasma enkephalinase activity occurs after
thirty minutes.
The bioavailability of racecadotril is not changed by food, but peak activity is delayed by approximately 1.5
hours.
Distribution:
Following oral administration of 14C-labelled racecadotril to healthy volunteers, a 200-fold increase in
racecadotril concentrations was recorded in the plasma compared to the blood cells, and a 3-fold increase
in the plasma versus total blood volume. There is no significant binding to blood cells.
In the plasma, the mean apparent volume of distribution of 66.4 L/kg demonstrates moderate distribution of 14C
in the 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, mainly albumin.
The pharmacokinetic properties of racecadotril do not alter during repeated dosing or in elderly subjects.
The extent and duration of action of racecadotril are dose-dependent. Peak plasma enkephalinase concentrations
are reached approximately 2 hours post-dose, corresponding to 75% inhibition for the dose of 100 mg.
Plasma enkephalinase activity continues for around 8 hours following the administration of 100 mg.

Biotransformation: 

The biological half-life of racecadotril, determined on the basis of enkephalinase plasma inhibition, is 3
hours.
Racecadotril is rapidly hydrolysed into tiorfan (RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine, its
active metabolite, which itself transforms into inactive metabolites S-methylthiorphan sulfoxide, S methyl
tiorfan, 2-methane sulfinylmethyl propionic acid and 2-methylsulfanylmethyl propionic acid, which are all
formed following more than 10% systemic exposure to the parent molecule.
Other minor metabolites have also been detected and quantified in the urine and faecal matter.
Repeated dosing with racecadotril does not cause accumulation in the body.
The in-vitro data show that racecadotril/tiorfan and its four major inactive metabolites do not significantly
inhibit cytochrome CYP 3A4 isoforms, 2D6, 2C9, 1A2 and 2C19.
The in-vitro data show that racecadotril/tiorfan and its four major inactive metabolites do not significantly
induce CYP cytochrome isoforms (family 3A, 2A6, 2B6, 2C9/2C19, family 1A, 2E1) and the enzymes
which bind to glucuronyl transferase.
Racecadotril does not change the protein binding of products which are strongly bound to proteins, such as
tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.
In patients with hepatic insufficiency (cirrhosis, Child-Pugh B), the metabolite’s kinetic profile displays the
same Tmax and T1/2 values and lower Cmax (-65%) and area under the curve (-29%) compared to healthy
subjects.
In patients with severe renal insufficiency (creatinine clearance between 11 and 39 ml/min), the metabolite’s
kinetic profile displays a lower Cmax (-49 %) and larger area under the curve (+15 %) and T1/2 compared to
healthy volunteers (creatinine clearance > 70 ml/min).
The pharmacodynamic results obtained in the paediatric population are similar to those of the adult
population, with Cmax being reached 2.5 hours post-dose. There is no accumulation following
administration of repeated doses every 8 hours, for 7 days.
Elimination:
Racecadotril is eliminated via its active and inactive metabolites. Elimination occurs primarily via the kidneys
(81.4%) and, to a lesser extent, in the faeces (about 8%). There is no significant elimination via the pulmonary
route (less than 1% of the dose).

Four-week chronic toxicity studies conducted in monkeys and dogs, which are beneficial for assessing the
duration of treatment in humans, did not highlight any effect at doses of up to 1,250 mg/kg/day and 200
mg/kg, which correspond to safety margins of 625 and 62, respectively (in relation to humans).
Racecadotril did not prove to be immunotoxic to mice treated for 1 month.
Longer exposure (one year) to monkeys revealed generalised infections and reduced antibody response on
vaccination (at a dose of 500 mg/kg/day) and no infection/immune suppression at 120 mg/kg/day.
Similarly, a few infectious/immune responses were noted in dogs receiving 200 mg/kg/day for 26 weeks.
The clinical significance is not known: see section 4.8.
No mutagenic or clastogenic effects of racecadotril were observed during standard in-vivo and in-vitro testing.
No carcinogenicity tests were conducted since treatment is administered short term.
Reproductive and development toxicity tests (pre-embryonic and fertility development, antenatal and postnatal
development, embryo-foetal development studies) have not revealed any racecadotril-specific effect.
Other preclinical effects (such as severe anaemia, probably aplastic, increased diuresis, ketonuria and
diarrhoea) were observed only after exposure sufficiently exceeding the maximum exposure in
humans. Their clinical significance is not known.
A toxicity study conducted in young rats did not reveal any evidence of a significant racecadotril-related effect
at doses up to 160 mg/kg/day, which is 35 times higher than the recommended paediatric dose (e.g. 4.5
mg/kg/day).
Despite immature renal function in children under 1 year old, higher levels of exposure are not expected in this
particular group.

No harmful effects on the central nervous system, cardiovascular system or respiratory function have
been highlighted in other pharmacology safety studies.
In animals, racecadotril potentiates the effect of butyl hyoscine on the intestinal tract and on the
anticonvulsant effect of phenytoin.

Lactose monohydrate, pregelatinised maize starch, magnesium stearate and colloidal anhydrous silica.
Composition of the capsule shell: gelatine, titanium dioxide (E171), yellow iron oxide (E172)

N/A.

This medicinal product does not require any special precautions for storage.

20 capsules in heat-formed blister strips (PVC-PVDC/aluminium).

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