Medication-Induced Diarrhea

Causative Medications

• Medications account for up to 4% of chronic diarrhea cases, with antibiotics responsible for 25% of all drug-induced diarrhea, followed by magnesium-containing antacids, non-steroidal anti-inflammatory drugs, antihypertensives, and chemotherapeutic agents 1, 2
• The American Gastroenterological Association notes that antibiotics cause diarrhea in 5-62% of patients through multiple mechanisms: alteration of intestinal microflora, osmotic diarrhea due to changes in carbohydrate metabolism, and altered absorption of short-chain fatty acids 3
• The Centers for Disease Control and Prevention recommend that recent antibiotic use should be actively investigated in any patient with diarrhea, especially if there is exposure to daycare or recent travel 4, 6
• The American Society of Clinical Oncology states that fluoropyrimidines (5-FU and capecitabine) cause diarrhea in 30-50% of patients, with severe diarrhea (grade 3-4) occurring in 10-20% 7, 8, 9
• The National Comprehensive Cancer Network notes that irinotecan causes two types of diarrhea: (1) acute immediate diarrhea due to cholinergic effects that responds to atropine 0.25-1 mg, and (2) late (after 24 hours) potentially life-threatening diarrhea, especially in combinations such as CapeIRI (47% grade 3-4) and FOLFIRI (14% grade 3-4) 7, 8, 9
• The European Society for Medical Oncology reports that taxanes cause diarrhea, with cabazitaxel causing diarrhea in 47% (6% grade 3), docetaxel in 19-47% (0-27% grade 3, higher in >65 years), and paclitaxel in 39% (3-7% grade 3) 7, 8, 9
• The American College of Cardiology recommends considering the use of anti-diarrheal medications in patients with heart failure who are taking medications that may cause diarrhea 1, 2
• The American Society of Health-System Pharmacists notes that gliptins (DPP-4 inhibitors) are newer agents associated with diarrhea 2

Patient Populations at Risk

• The American Geriatrics Society states that elderly patients consume proportionally more medications and have a higher risk due to decreased gastric acid production, reduced T cells, and lower secretory IgA 3
• The National Cancer Institute reports that chemotherapy causes diarrhea in 27-76% of neutropenic patients, but only 5-17% have an identifiable infectious cause 3
• The European Society for Medical Oncology notes that patients with DPD deficiency who receive 5-FU may experience potentially life-threatening complications, including severe diarrhea, mucositis, and pancytopenia 7, 9

Management of Medication-Induced Diarrhea

• The American Gastroenterological Association recommends suspending the offending medication when possible 3
• The American Society of Clinical Oncology states that loperamide 2 mg every 2 hours and 4 mg every 4 hours at night is effective for non-infectious chemotherapy-induced diarrhea 3
• The National Comprehensive Cancer Network notes that octreotide 500 μg three times a day subcutaneously may be used if loperamide fails, with dose escalation until symptoms are controlled 3, 10
• The Centers for Disease Control and Prevention recommend avoiding hyperosmolar foods, such as undiluted apple juice, gelatin, and pre-sweetened cereals, which can exacerbate osmotic diarrhea 4, 5