Prescription only.
Read the instructions thoroughly before use.
Please consult your physician for more information.
Keep out of reach and sight of children.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Active ingredient:
Racecadotril .................... 10 mg
Excipients: q.s …………….. 1 tablet
Granule for oral suspension.
Product description: The preparation contains white to off-white, dry, loose, fragrant granules.
Box of 24 sachets x 1.5 g
Pharmacotherapeutic group: Other antidiarrhoeals.
ATC code: A07XA04.
Racecadotril is a pro-drug that needs to be hydrolysed to its active metabolite thiorphan, which is an inhibitor of enkephalinase, a cell membrane peptidase enzyme located in various tissues, notably the epithelium of the small intestine. This enzyme contributes both to the digestion of exogenous peptides and to the breakdown of endogenous peptides such as enkephalins. Racecadotril protects enkephalins from enzymatic degradation thereby prolonging their action at enkephalinergic synapses in the small intestine and reducing hypersecretion.
Racecadotril is a pure intestinal antisecretory active substance. It decreases the intestinal hypersecretion of water and electrolytes induced by the cholera toxin or inflammation and does not have effects on basal secretory activity. Racecadotril exerts rapid antidiarrhoeal 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 diarrhoea and the need for rehydration was also observed.
An individual patient data meta-analysis (9 randomised clinical trials racecadotril versus placebo, in addition to oral rehydration solution) collected individual patient data from 1384 boys and girls suffering from acute diarrhoea of miscellaneous severity and treated as in- or out-patients The median age was 12 months (interquartile range: 6 to 39 months). A total of 714 patients were < 1 year and 670 patients were ≥ 1 year old. Mean weight ranged from 7.4 kg to to 12.2 kg across studies. The overall median diarrhoea duration after inclusion was 2.81 days for placebo and 1.75 days for racecadotril. The proportion of recovered patients was higher in racecadotril groups compared with placebo [Hazard Ratio (HR): 2.04; 95% CI: 1.85 to 2.32; p < 0.001; Cox Proportional Hazards Regression]. Results were very similar for infants (<1 year) (HR: 2.01; 95% CI: 1.71 to 2.36; p < 0.001) and toddlers (>1 year) (HR: 2.16; 95% CI: 1.83 to 2.57; p < 0.001). For inpatient studies (n=637 patients), the ratio of mean stool output racecadotril/placebo was 0.59 (95% CI: 0.51 to 0.74); p < 0.001). For outpatient studies (n = 695 patients), the ratio of the mean number of diarrhoeic stools racecadotril/placebo was 0.63 (95% CI: 0.47 to 0.85; p < 0.001).
Racecadotril does not produce abdominal distension. During its clinical development, 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.
Absorption
Following oral administration, racecadotril is rapidly absorbed.
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 kinetic profile is not modified by repeated administration. No changes in pharmacokinetics were found in the elderly.
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 a dose of 100 mg.
The duration of plasma enkephalinase inhibition is about 8 hours.
Metabolism
The half-life of racecadotril, measured as plasma enkephalinase inhibition, is approximately 3 hours.
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 vitro data indicate that racecadotril/thiorphan and the four major inactive metabolites do not inhibit the major CYP enzymes isoforms 3A4, 2D6, 2C9, 1A2 and 2C19 to an extent that would be clinically relevant.
In vitro data indicate that racecadotril/thiorphan and the four major inactive metabolites do not induce the CYP enzymes isoforms (3A family, 2A6, 2B6, 2C9/2C19, 1A family, 2E1) and UGTs conjugating enzymes to an extent that would be clinically relevant.
Racecadotril does not modify protein binding of active substances strongly bound to proteins, such as tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.
In patients with liver failure [cirrhosis, grade B of the Child-Pugh classification], the kinetic profile of the active metabolite of racecadotril showed similar Tmax and T½ and lesser Cmax (-65%) and AUC (-29%) as compared to healthy subjects.
In patients with severe renal failure (creatinine clearance 11-39 ml/min), the kinetic profile of the active metabolite of racecadotril showed smaller Cmax (-49%) and greater AUC (+16%) and T½ as compared to healthy volunteers (creatinine clearance >70 ml/min).
In the paediatric 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.
Excretion
Racecadotril is eliminated as active and inactive metabolites. Elimination is mainly via the renal route and to a much lesser extent via the faecal route. The pulmonary route is not significant.
Racecadotril has no or negligible influence on the ability to drive and use machines.
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, fertility, embryo-foetal development, childbirth/delivery 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, this medicinal product should not be administered to breastfeeding women.
Like all medicines, racecadotril can cause side effects, although not everybody gets them. If you get any possible side effects not listed in this leaflet, or any side effects that become severe, talk to your doctor or pharmacist.
The following adverse drug reactions listed below have occurred with racecadotril more often than with a placebo or have been reported during post-marketing surveillance.
The frequency of adverse reactions is defined using 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).
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 receiving racecadotril.
The frequency of these reactions is unknown but if they occur. Treatment with racecadotril should be discontinued and replaced with appropriate therapy. Patients should be known not to re-use racecadotril in these cases.
Please inform your doctor of all undesirable effects upon drug administration.
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.
Store in dry places, not exceeding 30°C, protect from light.
The administration of Hasec does not modify the usual rehydration regimens.
Rehydration is highly important in the management of acute diarrhoea in infants. The requirement for rehydration and route should be adapted to the age and weight of the patient and the stage and severity of the condition, specifically in case of serious or prolonged diarrhoea with significant vomiting or a lack of appetite. Additionally, it is important that regular feeding (including breastfeeding) is not interrupted and that adequate fluid intake is monitored.
The presence of bloody or purulent stools and fever may indicate the presence of invasive bacteria as a reason for diarrhoea, or the presence of other severe disease. Also, racecadotril has not been tested in antibiotic-associated diarrhoea. Therefore, racecadotril should not be administered under these conditions. Concomitant administration of racecadotril and an antibiotic in treatment of acute bacterial diarrhoea may be used as a supplemental therapy.
Chronic diarrhoea has not been sufficiently studied with this medicinal product. Also, racecadotril has not been tested in antibiotic-associated diarrhoea.
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.
Because of possible reduced bioavailability, the product must not be administered in cases of prolonged or uncontrolled vomiting.
Occurrence of skin reactions has been reported with the use of the 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.
Excipients
This medicine contains 10 mg of aspartame in each sachet. Aspartame is hydrolysed in the gastrointestinal tract when orally ingested. One of the major hydrolysis products is phenylalanine. Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age.
This medicine contains less than 1 mmol sodium (23 mg) per sachet, that is to say essentially ‘sodium-free’.
Hasec 30 is indicated for the complementary symptomatic treatment of acute diarrhoea in infants (older than 3 months) and in children together with oral rehydration.
If causal treatment is possible, racecadotril can be administered as a complementary treatment.
Do not use Hasec if your child is allergic (hypersensitive) to the active substance or to any of the excipients.
Patients who have reported angioedema with angiotensin-converting enzyme inhibitors (such as captopril, enalapril, lisinopril, perindopril, ramipril) should not take racecadotril.
Hasec 30 is administered via the oral route, together with oral rehydration (see Special warnings and precautions for use).
The recommended dose is determined according to body weight: 1.5 mg/kg per dose (corresponding to 1 to 2 sachets), three times daily at regular intervals.
In children from 13 kg to 27 kg: one 30 mg sachet 3 times daily.
In children of more than 27 kg: two 30 mg sachets 3 times daily.
Treatment should be continued until normal stools are recorded.
Treatment should not exceed 7 days.
Long-term administration of racecadotril is not recommended.
There are no clinical trials in infants less than 3 months of age.
Special populations:
There are no studies in infants or children with renal impairment or hepatic impairment (see Special warnings and precautions for use).
The granules can be added to food, dispersed in a glass of water (approximately 1 teaspoon), mixed well and followed by immediate administration.
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