A Comprehensive Narrative Review of Drug Interactions Between Traveler's Diarrhea Medications and Chronic Therapies: Implications for Clinical Practice

Abstract

Diarrhea is a common illness for travelers. Traveler's diarrhea is typically defined as experiencing at least three unformed stools per day during a stay abroad or within 10 days of returning from the destination. In this review, we consulted five databases, namely, Medicine Complete, Medscape, Drugs.com, Epocrates, and DDInter, to conduct a comprehensive drug interaction analysis. We selected commonly prescribed medications used for the treatment of traveler's diarrhea, including ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, azithromycin, rifaximin, bismuth salicylate, and loperamide. The antidiabetic medications chosen included metformin, glipizide, glimepiride, sitagliptin, linagliptin, dapagliflozin, empagliflozin, and acarbose. The chosen antihypertensive drugs were telmisartan, olmesartan, amlodipine, nifedipine, enalapril, ramipril, metoprolol, and propranolol. Aspirin, clopidogrel, ticagrelor, rivaroxaban, warfarin, atorvastatin, and rosuvastatin were also chosen as they play an essential role in cardiovascular treatment. We performed comprehensive interaction checks across all five databases for each combination of a traveler's diarrhea medication and medication from one of the three comorbid conditions (antidiabetic, antihypertensive, or cardioprotective). We categorized the severity of interactions as mild, moderate, or severe. Similarly, we used colors to highlight the number of databases reporting drug interactions, providing insights into the reliability of these interactions across sources. Interactions with antidiabetic drugs revealed that fluoroquinolones and sulfonylureas produce severe interaction effects. Comparatively, rifaximin can be safer as it exhibited mild interaction only with metformin, whereas the other antidiabetic drugs showed no interaction effect. Levofloxacin was found to be the safest drug among hypertensive individuals as it exerted no interaction effects with any of the antihypertensive medications. Levofloxacin and rifaximin were considered to be safe as these drugs interacted with only two cardioprotective drugs. This review features the importance of a precise approach in prescribing medications for traveler's diarrhea, especially for patients with chronic comorbidities. These findings play a pivotal role in improving awareness and providing tailored treatment for the interaction to ensure patient well-being.

Keywords: antidiabetic; antihypertensive; cardioprotective; drug interaction; traveler’s diarrhea.

Figure 1. Traveler’s diarrhea drugs vs. antidiabetic drugs.

The symbols and colors in the table denote different indications. *: mild interaction effects that imply no action is required. #: moderate interaction effects that mandate careful monitoring. $: severe interaction effects that suggest avoiding or using an alternate; green color: no interaction was identified; yellow color: interactions were discovered in a single database; orange color: interactions were identified in two databases; red color: interactions were detected in three to five databases

Figure 2. Traveler’s diarrhea drugs vs. antihypertensive drugs.

The symbols and colors in the table denote different indications. *: mild interaction effects that imply no action is required. #: moderate interaction effects that mandate careful monitoring. $: severe interaction effects that suggest avoiding or using an alternate; green color: no interaction was identified; yellow color: interactions were discovered in a single database; orange color: interactions were identified in two databases; red color: interactions were detected in three to five databases

Figure 3. Traveler’s diarrhea drugs vs. cardioprotective drugs.

The symbols and colors in the table denote different indications. *: mild interaction effects that imply no action is required. #: moderate interaction effects that mandate careful monitoring. $: severe interaction effects that suggest avoiding or using an alternate; green color: no interaction was identified; yellow color: interactions were discovered in a single database; orange color: interactions were identified in two databases; red color: interactions were detected in three to five databases