ACTION AND MECHANISM

Antidiarrheal and intestinal antisecretory agent. Racecadotril is a prodrug of thiophane, a true active metabolite, formed by hydrolysis. Thiorphane is a selective inhibitor of plasma enkephalinase, a membrane peptidase responsible for the degradation of natural enkephalins. The inhibitory effect on enkephalinase translates, at the level of the intestinal mucosa, into a sustained effect of enkephalins on delta-type opioid receptors, which are involved in the regulation of intestinal water and electrolyte reabsorption. The sustained action of enkephalins on these receptors is responsible for the intestinal antisecretory effect on water and electrolytes, neutralizing the hypersecretion induced by various agents, both chemical and biological. Inhibition of peripheral enkephalinase leads to an increase in the persistence of enkephalins, with the consequent regulatory effect on intestinal secretion. Racecadotril does not appear to significantly affect basal secretion or modify intestinal transit time. The action is exclusively peripheral (only 1% of the racecadotril dose is distributed into the tissues), with no significant effects observed on the central nervous system. Following oral administration, the enkephalinase inhibitory effect begins to manifest within 30 minutes, reaching maximum activity after two hours. With oral doses of 1.5 mg/kg, the maximum enzyme inhibition level is approximately 90%. The inhibitory effect is maintained significantly for around eight hours.

SPECIAL WARNINGS

- The administration of racecadotril does not modify the usual rehydration guidelines.

- It has not been sufficiently studied in chronic diarrhea. Racecadotril has not been studied in antibiotic-associated diarrhea.

PATIENT ADVICE

Treatment with Hidrasec should be discontinued if no clinical improvement is observed within 48 hours or if fever develops. A doctor should be consulted in these cases.

CONTRAINDICATIONS

- Hypersensitivity to the active ingredient or to any of the excipients.- Enteroinvasive diarrhea, characterized by fever and blood in the stools.- Diarrhea caused by antibiotic therapy.

PREGNANCY

Reproductive studies show no toxic effects on the fetus in the species studied (rats and rabbits). However, due to a lack of specific clinical studies, it should not be administered to pregnant women.

PHARMACOKINETICS

- Absorption: It is a prodrug, which, after oral administration, is completely hydrolyzed in peripheral tissues to thiophan (the active metabolite). Racecadotril is rapidly absorbed orally. Activity on plasma enkephalinase appears within 30 minutes. The duration and extent of the effect of racecadotril depend on the administered dose. Peak activity on plasma enkephalinase is observed approximately 2 hours after administration and corresponds to 90% inhibition with a dose of 1.5 mg/kg. The duration of inhibitory activity on plasma enkephalinase is approximately 8 hours. Food: Bioavailability is not altered if administered with food, but peak activity is delayed by approximately 1.5 hours. Distribution: Only 1% of the administered dose is distributed into the tissues. Ninety percent of the active metabolite of racecadotril, ((RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl)glycine, is bound to plasma proteins, primarily albumin. - Metabolism: It is rapidly hydrolyzed to ((RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl)glycine, the active metabolite, which is further transformed into inactive metabolites that are eliminated via the kidneys, feces, and lungs. - Elimination: The half-life is approximately 3 hours. The pharmacokinetic properties of racecadotril are not altered by repeated administration or in elderly patients.

INDICATIONS

* Without a prescription (Hidrasec):
- [ACUTE DIARRHEA]: Symptomatic treatment of nonspecific acute diarrhea in adults.

INTERACTIONS

- Butylscopolamine: In rodents, high doses (10-20 mg/kg orally) have resulted in a slight potentiation of the effects of butylscopolamine on gastrointestinal transit. - Phenytoin: In rodents, a slight potentiation of the anticonvulsant action has been observed.

LACTATION

Due to a lack of data on the passage of racecadotril into breast milk, it should not be administered to women during the breastfeeding period.

POSOLOGY

Oral route:

- Adults and the elderly: 100 mg initially, at any time of day; subsequently, 100 mg/8 h, preferably before main meals.

DOSAGE IN HEPATIC INSUFFICIENCY

* There is insufficient clinical experience.

DOSAGE IN RENAL INSUFFICIENCY

* There is insufficient clinical experience.

PRECAUTIONS

In cases of severe or prolonged diarrhea with significant vomiting or loss of appetite, intravenous rehydration should be considered. In cases of diarrhea with clinical manifestations suggesting an infectious etiology, antibacterial agents with good systemic diffusion should be administered. It should not be used in cases of renal or hepatic impairment due to a lack of data in these populations.

PRECAUTIONS RELATING TO EXCIPIENTS

This medicine contains lactose. Patients with hereditary lactose or galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

ADVERSE REACTIONS

The side effects described in the clinical trials occurred with a similar incidence to placebo. The most frequent were: - Gastrointestinal: [VOMITING] (5%), [CONSTIPATION] (<1%). - Other: [FEVER] (1.3%). - Dermatological: rarely, [EXANTHEMATOUS ERUPTIONS]. Frequency not known: [ERYTHEMA MULTIFORME], tongue edema, facial edema, angioedema, urticaria, erythema nodosum, papular rash. - Nervous system: Frequent: [HEADACHE]. Rarely, [VERTIGO].

OVERDOSE

- No cases of overdose have been reported. - Doses exceeding 2 g in a single administration, equivalent to 20 times the therapeutic dose, have been administered to adults without any observed adverse effects. Naloxone reverses the antidiarrheal effects of racecadotril.

COMPOSITION

RACECADOTRILO: 100 MILLIGRAMS
LACTOSE (EXCIPIENT): 41 MILLIGRAMS - MONOHYDRATE
CORN STARCH (EXCIPIENT): 0 - PREGELATINIZED