Racecadotril

BRAND NAMES

Racecadotril is sold under various brand names, including Redotil, Enuff, Hidrasec, Tiorfan, and Tiorfix. Some other brand names for racecadotril include Zedott, Racigyl, Racedot, and Ralop. 

MECHANISM OF ACTION

Racecadotril exerts its effect by inhibiting the intestinal enzyme enkephalinase, which prevents the breakdown of naturally occurring peptides called enkephalins. As a result, enkephalin levels rise and activate delta-opioid receptors in the gut, reducing the excessive secretion of water and electrolytes into the intestinal lumen. This mechanism allows racecadotril to decrease diarrhea without altering normal intestinal motility.

PHARMACOKINETICS

Absorption

Racecadotril is rapidly and well absorbed from the intestinal tract after oral administration. It is a prodrug that is quickly hydrolyzed into its active metabolite, thiorphan, which is responsible for the drug's therapeutic effects.

Distribution

The volume of distribution for racecadotril's main active metabolite, thiorphan, is approximately 66.4 L/kg. This indicates a large volume of distribution, meaning it is extensively distributed into body tissues rather than remaining primarily in the bloodstream. 

Metabolism

Racecadotril is a prodrug that is rapidly metabolized in the body to its active form, thiorphan, primarily in the liver and intestinal mucosa. Thiorphan is responsible for the drug’s antisecretory effects by inhibiting enkephalinase in the gut. The metabolism of racecadotril is mainly hepatic, involving hydrolysis, and it does not undergo significant involvement of the cytochrome P450 system, which reduces the potential for drug–drug interactions. The metabolites, including thiorphan, are eventually excreted in the urine and feces, with the parent compound being only minimally detectable in systemic circulation.

Excretion

Racecadotril and its metabolites are primarily eliminated via the kidneys (urine), which accounts for approximately 81.4% of the excretion. A much smaller amount is eliminated in the feces, around 8%. 

PHARMACODYNAMICS

Racecadotril’s pharmacodynamic effects result from its conversion into the active metabolite thiorphan, which inhibits the enzyme enkephalinase. This inhibition elevates levels of endogenous enkephalins in the gut, reducing excessive secretion of water and electrolytes and thereby alleviating diarrhea without altering intestinal motility or transit time. The antisecretory effect is dose-dependent, reaches its maximum approximately two hours after administration, and thiorphan has an elimination half-life of about three hours.

ADMINISTRATION

Racecadotril is usually administered orally in the form of capsules, sachets, or granules, depending on the formulation. The medication is typically taken three times daily, ideally at the onset of diarrhea. It can be taken with or without food, and for pediatric use, sachets or granules can be mixed with a small amount of water or breast milk for easier administration. The duration of treatment generally continues until diarrhea resolves, usually 3–7 days, but should follow medical guidance.

DOSAGE AND STRENGTH

Adults:

100 mg orally, three times daily at the onset of diarrhea.

Children:

• <1 year: 10 mg/kg/day divided into 3 doses

• 1–12 years: 30 mg three times daily

• >12 years: 100 mg three times daily

Formulations/Strengths:

• Capsules: 100 mg

• Granules or sachets: 10 mg/kg or premeasured doses for children

Note:

• The dose may be adjusted according to age and weight in pediatric patients.

• Treatment is generally continued until diarrhea resolves, usually up to 7 days.

DRUG INTERACTIONS

Racecadotril has a low risk of drug interactions because it is mainly metabolized by hydrolysis, not CYP450 enzymes. It is generally safe with other antidiarrheals, opioids, or most medications, though caution is advised with electrolyte-altering drugs.

FOOD INTERACTIONS

Racecadotril has no significant food interactions and can be taken with or without food as directed by a physician. Taking it with food may slightly delay peak activity by 1–1.5 hours, and some sources suggest administering it before main meals to optimize absorption.

CONTRAINDICATIONS

• Hypersensitivity: Known allergy to racecadotril or any component of the formulation.

• Neonates: Particularly in premature infants, due to limited safety data.

• Severe dehydration or shock: Requires rehydration first, as racecadotril does not replace fluid loss.

• Obstruction of the gastrointestinal tract: Risk of worsening the condition.

• Chronic diarrhea of unknown origin: Use is contraindicated until the cause is identified.

SIDE EFFECTS

Common Side Effects

• Headache

• Skin rash (including redness, itching, urticaria)

• Nausea/Vomiting

• Dizziness

• Tonsillitis (particularly in children) 

• Serious Side Effects (Rare)

• Angioedema: Swelling of the face, lips, tongue, or throat, which may cause difficulty breathing.

• Severe skin reactions: Such as erythema multiforme or erythema nodosum.

• Anaphylaxis: A severe, whole-body allergic reaction.

• Hypersensitivity reactions: A combination of fever, rash, and inflammation of internal organs. 

OVERDOSE

No cases of fatal or severe overdose with racecadotril have been reported in humans. Adults have tolerated doses as high as 20 times the recommended therapeutic amount for example, a single 2000 mg dose or 400 mg taken three times daily for a week without serious adverse effects. Potential overdose symptoms may include severe headache or enhanced gastrointestinal side effects such as nausea or vomiting, though serious reactions are uncommon.

TOXICITY

Racecadotril has a low risk of toxicity when used at recommended doses. Overdose is uncommon, and adults have tolerated amounts up to 20 times the therapeutic dose without serious adverse effects. Its main safety concerns relate to pre-existing conditions or rare side effects, rather than general toxicity in healthy individuals.