Racecadotril

Racecadotril is an antidiarrheal agent that acts as a peripheral enkephalinase inhibitor. It also belongs to the group of opioids . It is used for the symptomatic treatment of diarrhea.

It is available in Europe and in most South American and some Southeast Asian countries, but not in the United States. It was first approved in 2007.

Pharmacodynamics

Enkephalins are endogenous peptides that bind to opioid receptors and have a particularly high affinity for the δ-subtype. Activation of the δ-receptors inhibits the enzyme adenylyl cyclase, resulting in a decrease in intracellular levels of the neurotransmitter cAMP. This reduces diarrhea-induced hypersecretion in the small intestine. Enkephalinase enzymes normally rapidly degrade enkephalin. In particular, the active metabolite of the drug, thiorphan, but also racecadotril itself, inhibit enkephalinase in the intestinal epithelium and protect enkephalins from degradation by these enzymes. This significantly prolongs the action of enkephalins and reduces diarrhea symptoms.

Inhibition of enkephalinases begins about 30 minutes after administration, reaches its maximum about two hours after administration, and persists for eight hours.

Pharmacokinetics

Racecadotril is rapidly absorbed after oral administration and reaches maximum plasma concentration within 60 minutes. Food ingestion delays the time to this maximum by 60 to 90 minutes, but has no effect on overall bioavailability. Racecadotril is rapidly and effectively metabolized in the liver to the major active metabolite, thiorphan. 90% of the substance is bound to blood plasma proteins. The elimination half-life, as measured by enkephalinase inhibition, is three hours. Thiorphan is then further metabolized to inactive metabolites. Both active and inactive metabolites are excreted largely by the kidneys (81.4%) and to a lesser extent by the feces (8%).

Drug Interactions

The drug has a very low potential for interaction with other drugs. The combination of racecadotril with an ACE inhibitor may theoretically increase the risk of angioedema.

Side effects

The most common adverse effect is headache, which occurs in only 1-2% of patients. Skin rashes occur in less than 1% of patients.

Other rarely occurring side effects include:

• Nausea
• Abdominal pain
• Vomiting
• Fever
• Hypokalemia
• Constipation
• Meteorism

Contraindications

There are no contraindications for racecadotril except for known hypersensitivity to the active ingredient.