Racecadotril

Racecadotril is an enkephalinase inhibitor that reduces intestinal hypersecretion without slowing gut transit. It is used as an adjunct to oral rehydration in acute watery diarrhoea, particularly in children, and it does not cause constipation or ileus.

Classification. Antisecretory antidiarrhoeal; enkephalinase inhibitor.

Mechanism. Its active metabolite thiorphan inhibits enkephalinase, increasing the half-life of endogenous enkephalins at delta-opioid receptors in the gut. This reduces cyclic AMP-driven secretion of water and electrolytes without altering motility.

Pharmacodynamics. Onset within 30 minutes to 1 hour; duration about 8 hours. It reduces stool output in acute watery diarrhoea by about one third.

Pharmacokinetics. Rapidly hydrolysed after oral absorption to thiorphan. Half-life of thiorphan about 3 hours. Protein binding about 90%.

Metabolism. Thiorphan is further metabolised to inactive metabolites and excreted mainly in urine.

Oral doses. Always give with oral rehydration solution and usual feeding; it does not replace rehydration.

Acute watery diarrhoea in adults. 100 mg three times daily, preferably before meals, until diarrhoea stops; maximum 7 days.

Acute watery diarrhoea in children (age over 3 months).

• 1.5 mg/kg three times daily, preferably before meals.

• Typical granule sachet doses: under 9 kg 10 mg; 9 to 13 kg 20 mg; 13 to 27 kg 30 mg; over 27 kg 60 mg, each three times daily.

• Maximum 7 days, stopping when stool becomes normal.

Kidney and liver adjustment. No data in severe impairment; use with caution.

Contraindications. Hypersensitivity; hereditary fructose intolerance, glucose and galactose malabsorption, or sucrase-isomaltase deficiency (products contain sucrose); children under 3 months.

Common adverse effects. Headache and mild rash.

Serious adverse effects.

• Angioedema of the face, lips or tongue, particularly with ACE inhibitors.

• Erythema nodosum, urticaria and rare severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Major interactions.

• ACE inhibitors: increased risk of angioedema through additive reduced breakdown of bradykinin and substance P.

• No clinically important cytochrome P450 interactions.

Special groups.

• Pregnancy: no adequate data; avoid.

• Breastfeeding: no data; avoid.

• Children: licensed from 3 months for acute watery diarrhoea.

• Older adults: no adjustment.

• Kidney impairment: use with caution.

• Liver impairment: use with caution.

• Regional: availability varies in East Africa; oral rehydration solution and zinc remain the first-line treatment for children.

Formulations. Capsules 100 mg; granules for oral suspension 10 mg and 30 mg sachets.

Administration.

• Swallow capsules whole with water, before meals.

• Mix granules in food, water or a bottle feed and stir before giving.

• Do not use for chronic diarrhoea or antibiotic-associated diarrhoea.

Baseline. Hydration status; exclusion of blood in stool and high fever; review of ACE inhibitor use.

Monitoring.

• Hydration, stool frequency and volume.

• Skin and mucosal reactions.

• Review at 48 hours.

Therapeutic drug monitoring. Not applicable.

Stopping. Stop when stool becomes normal, or after 7 days at most. Stop at once for angioedema or severe skin reaction.

Referral and escalation. Admit for severe dehydration, bloody diarrhoea, high fever, persistent vomiting or diarrhoea lasting beyond 7 days. Evaluate for infection and malabsorption.