Racecadotril

Registered South African indications:

• Acute diarrhoea

Registered South African contraindications

Granules

• Hypersensitivity to the active ingredient or any of the excipients

Capsule

• Hypersensitivity to the active ingredient or any of the excipients
• Pregnancy
• Lactation

South African recommendations

Caution in the following patient groups

• Pregnancy (gra)
• Breastfeeding (gra)

Capsules and granules

Renal and hepatic impairment considerations

• No studies have been conducted among children suffering from renal or hepatic insufficiency. Due to the absence of data in cases of renal or hepatic insufficiency, racecadotril granules should not be administered
• Data is limited with regard to patients with renal insufficiency, therefore caution is advised in using racecadotril 100mg

Hypersensitivity and angioedema

• If the angioedema is associated with an obstruction of the upper respiratory passages, for example in the region of the tongue, the glottis, and/or of the larynx, emergency treatment should be administered rapidly
• Racecadotril must be interrupted and the patient put under close medical supervision, with initiation of appropriate follow-up until the complete and permanent disappearance of the symptoms
• Patients with antecedents of angioedema not associated with treatment by racecadotril may present an enhanced risk of developing angioedema
• Cases of hypersensitivity and Quincke's oedema have been reported among patients treated with racecadotril. These events may occur at any time in the course of the treatment (gra)

Cutaneous reactions

• Cutaneous reactions have been reported with the use of racecadotril
• In most cases, these reactions are slight and do not require treatment
• In certain situations however, these reactions can be severe and potentially life-threatening where a link with taking racecadotril cannot be excluded
• In the event of severe cutaneous reactions appearing, treatment must be immediately be stopped

Vomiting

• The bioavailability may be reduced among patients with prolonged vomiting
• In children, in the event of severe or prolonged diarrhoea, substantial vomiting, or refusal of food, rehydration by intravenous administration should be envisaged

Coadministration with enzyme conversion inhibitors (ACE inhibitors)

• The concomitant use of racecadotril and enzyme conversion inhibitors (ECI) can augment the risk of angioedema, therefore, a rigorous evaluation of the benefit/ risk ratio is necessary before initiating treatment with racecadotril among patients under treatment with enzyme conversion inhibitors

Effects on ability to drive and use machines

• Racecadotril is not likely to affect a child's ability to perform tasks requiring attention and has a negligible effect on the ability to drive or use machines

Capsules

Rehydration considerations in adults

• The administration of racecadotril does not modify usual rehydration regimens

Dysenteric syndrome

• In the presence of signs of an acute dysenteric syndrome, such as the presence of blood in the stool or a fever, racecadotril must not be used

Pseudomembranous collitis

• Racecadotril has not been evaluated, and must not be used, in the course of diarrhoea associated with antibiotics, including pseudomembranous colitis. There is not sufficient data relating to chronic diarrhoea in connection with this medicinal product

Lactose content in capsules

• Racecadotril capsules contains lactose
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take racecadotril capsules

Granules

Special considerations in children

• Racecadotril granules are only an adjuvant treatment, as a supplement to oral rehydration, and do not serve as a replacement for it
• Rehydration must be systematic among infants/children presenting with acute diarrhoea, in order to prevent or treat dehydration, and should be adjusted in such a way as to compensate for hydroelectric losses (See Additional Prescribing Points)

Invasive bacteria and severe disease

• Caution is advised in cases of severe or prolonged diarrhoea, substantial vomiting, or refusal of food, with a recommendation for intravenous rehydration if necessary
• Racecadotril is not recommended for diarrhoea associated with antibiotics due to lack of data
• The presence of blood or pus in stools, particularly with fever, may indicate invasive diarrhoea requiring antibacterial treatment

Saccharose content in granules

• This medicinal product contains saccharose 0.966g of saccharose per sachet. Its use is not recommended among patients presenting intolerance to fructose, glucose and galactose malabsorption syndrome, or sucrase/isomaltase deficit
• If the quantity of saccharose (source of glucose and of fructose) in the daily dose of this medicinal product exceeds 5g per day, this needs to be taken into account in the daily ration in cases of low-sugar diet or diabetes

Forms avail. in SA and covered in this monograph: cap

South African registered indications and dosages

Symptomatic treatment of acute nonspecific diarrhoea
- As a supplement to dietary measures

• Oral (cap): 100mg, 8hrly at meal times; Treatment duration: Continue until 2 solid stools are obtained, or 7 days, whichever comes first

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The capsules must not be chewed, opened or crushed

Paed. forms avail. in SA and covered in this monograph: gra

South African registered indications and dosages

Symptomatic treatment of acute diarrhoea
- As a supplement to oral rehydration

Younger than 3 months

• Not established for use

Older than 3 months

• Oral (gra): Usual dose established as a function of body weight: Initial: 1.5mg/kg; Then; 1.5mg/kg/dose divided into 3 administrations throughout the day; Treatment duration: Continue until 2 consistent solid stools are obtained without exceeding 7 days (see below table for use in practice)

For infants/children with body mass (kg)	Dosage
<9kg	10mg, 3 times dly
9kg to <13kg	20mg, 3 times dly
13kg to <27kg	30mg, 3 times dly
>27kg	60mg, 3 times dly

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The amount of rehydration by oral rehydration solute or by intravenous administration should be adjusted as a function of the intensity of the diarrhoea, the age, and the particular circumstances of the child (associated disorders, etc)

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The 10mg granules are indicated for infants from 3 months of age and less than 13kg in weight. The 30mg granules are indicated in children weighing 13kg or more

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The powder can be poured into food, either in a glass of water or in a feed bottle, stirring thoroughly and making use of the whole of the mixture immediately

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See additional prescribing points for considerations in children

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The capsules are not suitable for paediatric use

Pregnancy

South African recommendations

• Contraindicated (cap)
• Caution; not recommended (gra)
• Safety of the capsules in pregnancy has not been established and is contraindicated in pregnancy
• The granules are intended for use in young children and is not indicated for use in adults
• Animal studies have not revealed any direct or indirect harmful effect with regard to toxicity affecting reproduction. Clinical data on the use of racecadotril in the course of pregnancy is very limited. Therefore, racecadotril should be avoided during pregnancy

Breastfeeding

South African recommendations

• Contraindicated (cap)
• Caution; not recommended (gra)
• Women on treatment with racecadotril 100mg should not breastfeed their babies
• In the absence of data regarding the passing of racecadotril into mother's milk, and due to its pharmacological properties and the immaturity of the digestive tract of the neonate, administration should be avoided in the course of breastfeeding

Fertility

South African recommendations

• No effect on fertility has been observed during fertility studies conducted among male and female rats

South African recommendations

Capsules

• Caution; no dose adjustment recommended
  Data is limited with regard to patients with renal insufficiency. Caution is advised in using racecadotril 100mg

Granules

• Caution; not recommended
  No studies have been conducted among children suffering from renal insufficiency
  Due to the absence of data in cases of renal insufficiency, racecadotril should not be administered

South African recommendations

Capsules

• Caution; no dose adjustment recommended
  Data is limited with regard to patients with hepatic insufficiency. Caution is advised in using racecadotril 100mg

Granules

• Caution; not recommended
  No studies have been conducted among children suffering from hepatic insufficiency
  Due to the absence of data in cases of hepatic insufficiency, racecadotril should not be administered

South African recommendations

• No dose adjustment recommended

Nervous System Disorders

Common

• Headache (cap)

Skin and Subcutaneous Tissue Disorders

Uncommon

• Rash
• Erythema

Unknown

• Urticaria
• Angioedema
• Quinicke's oedema
• Oedema of the tongue
• Oedema of the face
• Oedema of the lips
• Oedema of the eyelids
• Polymorphous erythema
• Erythema nodosum
• Papular rash
• Prurigo
• Pruritus
• Toxidermia (cap)

• Enzyme conversion inhibitors (ECI)
• ACE inhibitors
• Captopril
• Enalapril
• Lisinopril
• Perindopril
• Ramipril

• Fluid intake

Considerations in children

• Racecadotril granules is only an adjuvant treatment, as a supplement to oral rehydration, and does not serve as a replacement for it
• Rehydration must be systematic among infants/children presenting with acute diarrhoea, in order to prevent or treat dehydration, and should be adjusted in such a way as to compensate for hydroelectric losses
• The treatment for cases of acute diarrhoea among children is based essentially on the correction of losses of water and electrolytes by the use of oral rehydration solutes and early resumption of feeding, the forms of which depend on the age of the child and the type of feeding prior to the diarrhoea
• In the event of severe or prolonged diarrhoea, substantial vomiting, or refusal of food, rehydration by intravenous administration should be envisaged
• The presence of blood or pus in the stool, with fever, could be a sign of diarrhoea with invasive germs or the presence of other disorders in progress. In cases of infectious diarrhoea with clinical signs suggestive of an invasive phenomenon, recourse should be made to antibacterial agents with good systemic distribution
• Racecadotril has not been evaluated in the course of diarrhoea associated with antibiotics, and should therefore not be used in these cases
• Due to a potentially reduced bioavailability, racecadotril should not be administered in cases of prolonged or uncontrollable vomiting

Racecadotril is a prodrug which must be hydrolysed to its active metabolite thiorphan, which is an inhibitor of enkephalinase, an enzyme of the cellular membrane, present in different tissues, among them the intestinal epithelium. This enzyme contributes to the hydrolysis of exogenic and endogenic peptides, such as enkephalins. Racecadotril accordingly protects the enkephalins against enzymatic degradation, thereby prolonging their action at the level of the enkephalinergic synapses of the small intestine, thereby reducing hypersecretion. Racecadotril is a pure anti-intestinal secretion substance. It reduces the intestinal hypersecretion of water and electrolytes induced by cholera toxin or inflammation, without change to intestinal transit time. In two clinical studies carried out among children, racecadotril reduced the weight of the stool by 40% and 46% respectively, within the first 48 hours. A significant reduction in the duration of the diarrhoea and of the need for rehydration has likewise been observed

Capsule 100 mg

• Hidrasec ( Abbott Laboratories)

Granules (per sachet) 30 mg

• Hidrasec ( Abbott Laboratories)