Under normal circumstances, loperamide has minimal systemic absorption due to extensive first-pass metabolism and limited permeability across the intestinal mucosa. However, in the presence of severe gastrointestinal inflammation, compromised mucosal integrity may enhance loperamide’s central opioid effects via altered pharmacokinetics. Although respiratory depression due to therapeutic loperamide use remains sparse, this case accentuates the risks in vulnerable patients. This case report describes a rare case of loperamide-induced respiratory depression in a patient with chemotherapy-induced gastrointestinal mucosal inflammation, and highlights the potential increased systemic absorption and opioid-like toxicity in vulnerable patients receiving high-dose loperamide therapy. A 75-year-old female who was undergoing active chemotherapy developed significant diarrhoea. Endoscopy revealed active inflammation from the oesophagus to the large bowel. She was treated with high-dose loperamide and octreotide. Subsequently, she developed respiratory depression and altered consciousness, which resolved rapidly with naloxone infusion without lasting effects. In such settings, clinicians should exercise caution with high-dose loperamide as compromised mucosal barriers can facilitate systemic drug accumulation and toxicity.
Thong et al. (Sat,) studied this question.