Associated with adverse drug interactions - diarrhoea

Red flags

Diarrhoea + fever + abdominal pain after antibiotics - C. difficile / pseudomembranous colitis
Bloody diarrhoea with drug exposure (mycophenolate, NSAIDs, ICI colitis)
Severe dehydration, haemodynamic compromise
Diarrhoea in a patient on an immune checkpoint inhibitor - possible colitis, can be severe/life-threatening

Antibiotic-associated

Broad-spectrum antibiotics (clindamycin classically, but any) -> dysbiosis -> C. difficile colitis
Direct osmotic/motility effect of the antibiotic itself (amoxicillin-clavulanate common)

Direct GI toxicity

Metformin (dose-dependent, common, often improves with slow titration/XR formulation)
Chemotherapy (irinotecan - cholinergic acute type and delayed type), targeted therapy (EGFR inhibitors)
Immune checkpoint inhibitor colitis - can mimic IBD, needs steroids +/- biologic if severe
Magnesium-containing antacids/laxatives
Orlistat (fat malabsorption)
SSRIs (early, usually transient)
Mycophenolate (dose-dependent enterocolitis)
Colchicine (early toxicity sign, dose-related)

Withdrawal

Antibiotic exposure in preceding weeks (C. diff risk persists for weeks after cessation)
Timing relative to new drug/dose
Immunosuppression, cancer therapy, recent hospitalisation
Blood/mucus in stool, systemic symptoms

Stop the causative/precipitating agent where feasible
C. difficile: stop inciting antibiotic if possible; oral vancomycin or fidaxomicin first-line (metronidazole reserved for mild disease where the others are unavailable); faecal microbiota transplant for recurrent disease
Metformin-associated - slow dose titration, switch to XR formulation, take with food
ICI colitis: grade-based - withhold ICI, corticosteroids for grade >=2, infliximab or vedolizumab for steroid-refractory
Avoid loperamide in suspected C. difficile/infective colitis (risk of toxic megacolon)
Fluid and electrolyte replacement

C. difficile risk persists for weeks after the antibiotic course finishes - easily missed if only recent medications are reviewed
Loperamide can precipitate toxic megacolon in C. difficile colitis - avoid
ICI colitis can occur months after starting therapy and mimic infective colitis - always ask about immunotherapy history
Metformin-associated diarrhoea is dose-related and often solved by switching to extended-release rather than stopping the drug

1. Antibiotic history extends beyond "current medications"

"C. difficile risk outlasts the antibiotic course by weeks, so I ask about anything in the last 2-3 months."

2. Don't reach for loperamide reflexively

"In suspected infective or C. difficile colitis, anti-motility agents can precipitate toxic megacolon."

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