Usage
- Racecadotril is prescribed for the symptomatic treatment of acute diarrhea in adults and children over three months of age. It is used as an adjunctive therapy to oral rehydration when rehydration alone is insufficient. In cases where the cause of diarrhea can be treated directly, racecadotril can be used as a complementary treatment.
- Pharmacological Classification: Antidiarrheal, Enkephalinase inhibitor
- Mechanism of Action: Racecadotril is a prodrug that is rapidly hydrolyzed to its active metabolite, thiorphan. Thiorphan inhibits enkephalinase, a membrane-bound peptidase found in the brush border of the small intestine. Enkephalinase degrades enkephalins, naturally occurring opioid peptides. By inhibiting enkephalinase, racecadotril increases the concentration of enkephalins in the gut. Enkephalins decrease intestinal secretions, thereby reducing the loss of water and electrolytes in the stool.
Alternate Names
- Acetorphan
- Tiorfan
- Hidrasec
- Tiorfix
- Tiorfast
How It Works
- Pharmacodynamics: Racecadotril reduces intestinal hypersecretion by inhibiting enkephalinase, thus reducing the volume and frequency of stools in acute diarrhea. It does not affect bowel transit time.
- Pharmacokinetics:
- Absorption: Racecadotril is well-absorbed orally and rapidly converted to its active metabolite, thiorphan.
- Metabolism: Rapidly metabolized to the active metabolite thiorphan.
- Elimination: Thiorphan is eliminated primarily through the kidneys. The half-life is approximately 3 hours.
- Mode of Action: Racecadotril, via its active metabolite thiorphan, inhibits the enzyme enkephalinase, which is responsible for degrading enkephalins in the small intestine. The increased concentration of enkephalins reduces intestinal fluid secretion without affecting basal intestinal motility.
- Receptor Binding/Enzyme Inhibition: Inhibits enkephalinase, an enzyme that breaks down enkephalins.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 100 mg regardless of the time of day.
- Maintenance dose: 100 mg three times daily, preferably before meals.
- Maximum daily dose: 400 mg
- Duration of treatment: Continue until two normal stools are recorded, not to exceed 7 days.
Children:
- Dosage is weight-based: 1.5 mg/kg per dose, three times daily.
- Infants (>3 months) <9 kg: 10 mg three times daily
- Infants 9- <13 kg: 20 mg three times daily
- Children 13-27 kg: 30 mg three times daily
- Children >27 kg: 60 mg three times daily (may use adult capsule formulation if appropriate).
- Maximum daily dose: Approximately 6 mg/kg
- Duration of treatment: Continue until two normal stools are recorded, not to exceed 7 days.
- Pediatric Safety Considerations: Not recommended for children under three months of age.
Special Cases:
- Elderly Patients: No dose adjustment is generally necessary. Exercise caution.
- Patients with Renal Impairment: Use with caution; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with chronic diarrhea, antibiotic-associated diarrhea, and a history of angioedema with ACE inhibitors.
Clinical Use Cases
Racecadotril’s use is limited to the management of acute diarrhea and is not indicated for the clinical settings listed (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations).
Dosage Adjustments
Dose adjustments may be needed in patients with renal or hepatic impairment.
Side Effects
Common Side Effects
- Headache
- Rash
- Skin redness (erythema)
- Tonsillitis (especially in children)
Rare but Serious Side Effects
- Angioedema
- Anaphylaxis
- Severe skin reactions (e.g., erythema multiforme, erythema nodosum)
- Hypersensitivity reactions
Long-Term Effects
No long-term adverse effects have been reported as the drug is typically used for a short duration.
Adverse Drug Reactions (ADR)
- Angioedema
- Anaphylaxis
- Severe skin reactions
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to racecadotril or any of its components.
- Patients who have experienced angioedema with ACE inhibitors.
- Diarrhea associated with fever, blood, or pus in the stool.
- Antibiotic-associated diarrhea.
- Chronic diarrhea.
- Children under three months old.
- Hereditary fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency (for formulations containing sugar).
Drug Interactions
- ACE inhibitors: Increased risk of angioedema.
- Pethidine: Increased risk or severity of adverse effects.
- Loperamide: Concurrent use may increase the risk of constipation.
- No significant interactions with CYP450 enzymes are known.
Pregnancy and Breastfeeding
- Racecadotril is not recommended during pregnancy or breastfeeding due to limited safety data. Consult with a healthcare provider to assess the potential risks and benefits.
Drug Profile Summary
- Mechanism of Action: Inhibits enkephalinase, increasing enkephalin concentrations and reducing intestinal secretions.
- Side Effects: Headache, rash, erythema, tonsillitis, angioedema (rare), anaphylaxis (rare).
- Contraindications: Hypersensitivity, history of angioedema with ACE inhibitors, severe diarrhea, chronic diarrhea, infants under 3 months.
- Drug Interactions: ACE inhibitors, Pethidine.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 100 mg TID (max 400 mg/day); Children: 1.5 mg/kg TID (max 6 mg/kg/day).
- Monitoring Parameters: Frequency and consistency of stools, hydration status.
Popular Combinations
Racecadotril is typically used alone with oral rehydration therapy. No specific drug combinations are routinely recommended.
Precautions
- General Precautions: Assess for contraindications, allergies, renal and hepatic function. Monitor for side effects.
- Pregnant Women: Avoid use.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Use with caution in elderly patients and children over 3 months. Not for use in infants under 3 months.
- Lifestyle Considerations: Alcohol should be avoided. No driving restrictions are typically necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Racecadotril?
A: Adults: 100 mg three times daily (max 400 mg/day). Children: 1.5 mg/kg three times daily (max 6 mg/kg/day).
Q2: How does Racecadotril work?
A: It inhibits enkephalinase, reducing intestinal secretions and thereby decreasing the frequency and volume of stools.
Q3: What are the common side effects?
A: Headache, skin rash, and redness are the most common side effects.
Q4: Is Racecadotril safe for pregnant or breastfeeding women?
A: It is generally not recommended due to limited safety data.
Q5: Can Racecadotril be used in children?
A: Yes, in children older than three months. The dose is weight-based: 1.5 mg/kg, three times daily.
Q6: How long should Racecadotril be taken?
A: Until diarrhea subsides (typically indicated by two normal stools), not to exceed 7 days.
Q7: What should I do if the diarrhea doesn’t improve?
A: Consult a doctor if diarrhea persists for more than 7 days despite treatment.
Q8: Are there any drug interactions I should be aware of?
A: Yes. Concurrent use with ACE inhibitors can increase the risk of angioedema. Concomitant use with Pethidine can increase the risk or severity of adverse effects. Concurrent use with Loperamide may increase the risk of constipation.
Q9: Can Racecadotril be taken with food?
A: Yes, it can be taken with or without food. Granules can be mixed with food or dispersed in water.
Q10: Should patients continue oral rehydration therapy while taking Racecadotril?
A: Yes, oral rehydration is essential in managing acute diarrhea and should be continued alongside Racecadotril.
