Comedication and Drug Interactions in Functional Gastrointestinal Disorders

Functional gastrointestinal disorders (called also disorders of the gut-brain interaction) such as functional dyspepsia and irritable bowel syndrome are highly common chronic gastrointestinal disorders, with a significant negative impact on the quality of life. The management of these disorders remains largely symptomatic, the pharmacological treatments including prokinetic and antiemetic agents such as domperidone and metoclopramide, antidiarrheals such as loperamide, antispasmodics, probiotics, antidepressants, and newer medications for irritable bowel syndrome with diarrhea such as eluxadoline and rifaximine. For some of these drugs, potentially hazardous drug interactions with undesirable and even life-threatening clinical outcomes are discussed in this chapter. To name a few, domperidone concurrent use with potent CYP3A4 inhibitors or with drugs that prolong the QT interval is expected to lead to serious cardiac outcomes. Coadministration of metoclopramide with serotoninergic antidepressants and neuroleptics can be associated with extrapyramidal symptoms. Tricyclic antidepressants and selective serotonin reuptake inhibitors are associated with increased risk of cardiotoxicity when coadministered with other drugs with effect on QT interval and with increased risk of serotonin syndrome when coadministered with drugs with serotoninergic effects.