Gastrointestinal Toxicity: Diarrhea and Colitis

Grading Toxicity

Diarrhea (increased frequency, loose, large volume, or liquidy stools)

  • Increase of <4 stools/day over baseline
  • Mild increase in ostomy output compared with baseline
  • Increase of 4–6 stools/day over baseline
  • Moderate increase of output in ostomy compared with baseline
  • Increase of ≥7 stools/day over baseline; incontinence
  • Hospitalization indicated
  • Severe increase in ostomy output compared with baseline
  • Limiting self-care ADLs
  • Life-threatening (e.g., perforation, bleeding, ischemic necrosis, toxic megacolon)
  • Urgent intervention required

Colitis (inflammation of the intestinal lining)

  • Asymptomatic; clinical or diagnostic observation only; intervention not indicated
  • Abdominal pain; blood or mucus in stool
  • Severe abdominal pain; change in bowel habits; medical intervention indicated; peritoneal signs
  • Life-threatening (e.g., hemodynamic collapse); urgent intervention indicated

Management (including Anticipatory Guidance)

Overall Strategy:

  • Rule out infectious, non-infectious, disease-related etiologies
  • May continue immunotherapy

Diet modifications (very important):

  • Institute bland diet; decrease fiber, uncooked fruits/vegetables, red meats, fats, dairy, oil, caffeine, alcohol, sugar
  • Send stool sample for C difficile testing, culture, and ova and parasite
  • Immunotherapy to be withheld until Grade ≤1 or patient’s baseline (ipilimumab, pembrolizumab, nivolumab)
  • Provide anti-diarrheals: Imodium® (loperamide) or Lomotil® (diphenoxylate/atropine)
  • If upper or lower GI symptoms persist >5–7 days
    • Oral steroids* to be started (prednisone 0.5 mg–1 mg/kg/day or equivalent)
    • After control of symptoms, a ≥4-week steroid* taper will be initiated
  • Immunotherapy to be discontinued if Grade 2 symptoms persist ≥6 weeks (ipilimumab) or ≥12 weeks (pembrolizumab, nivolumab), or for inability to reduce steroid dose to ≤7.5 mg (ipilimumab) or ≤10 mg prednisone or equivalent (pembrolizumab, nivolumab) within 12 weeks

Diet modification:

  • Institute bland diet low in fiber, residue, and fat (BRAT [Bananas, Rice, Applesauce, Toast] diet)
  • Decrease fiber, uncooked fruit and vegetables, red meats, fats, dairy, oil, caffeine, alcohol, sugar
  • Avoid laxatives or stool softeners
  • Advance diet slowly as steroids are tapered,* reduced to low doses and assess for loose or liquid stool for several days or longer
  • Steroids* to be tapered slowly over at least 4 weeks

(Moderate) persistent or relapsed symptoms with steroid* taper

  • Consider gastroenterology consult for possible intervention (flex sig/colonoscopy/endoscopy)
  • IV steroids* to be started at 1 mg/kg/day
  • Immunotherapy to be held until ≤Grade 1
  • Control symptoms, then ≥4-week steroid* taper
  • Recurrent diarrhea is more likely when treatment is restarted
  • Onset:
    • Continued diet modification, anti-diarrheals, and steroid titration
  • Immunotherapy:
    • Grade 3: Pembrolizumab or nivolumab to be withheld when used as single agent; ipilimumab to be discontinued as single agent and nivolumab when given with ipilimumab
    • Grade 4: Ipilimumab and/or PD-1 inhibitor to be discontinued
  • Dosage of steroids* to be increased:
    • Steroids* 1-2 mg/kg/day prednisone or equivalent: methylprednisolone (Solu-Medrol®) 1 g IV (daily divided) doses
  • Hospitalization
  • GI consultation
  • Assess for peritoneal signs, perforation (NPO & abdominal x-ray, surgical consult prn)
  • Use caution with analgesics (opioids) and anti-diarrheal medications

Steroid* refractory: (if not responsive within 72 hours to high-dose IV steroid* infusion)

  • Infliximab (Remicade®) 5 mg/kg infusion may be considered
  • May require ≥1 infusion to manage symptoms (may re-administer at week 2 & week 6)
  • Avoid with bowel perforation or sepsis
  • PPD (tuberculin) testing not required in this setting
  • Infliximab infusion delay may have life-threatening consequences

Diet modification:

  • Very strict with acute symptoms: clear liquids; very bland, low fiber and low residue (BRAT) diet
  • Advance diet slowly as steroids* reduced to low doses
  • Steroids* to be tapered slowly over at least 4 weeks
  • Supportive medications for symptomatic management:
    • Loperamide: 2 capsules at the onset & 1 with each diarrhea stool thereafter, with a maximum of 6 per day
    • Diphenoxylate/atropine 1-4 tablets per day
    • Simethicone when necessary

Nursing Implementation:

  • Compare baseline assessment: grade & document bowel frequency
  • Early identification and evaluation of patient symptoms
  • Grade symptom & determine level of care and interventions required
  • Early intervention with lab work and office visit if colitis symptoms are suspected

*Steroid taper instructions/calendar as a guide but not an absolute

  • Taper should consider patient’s current symptom profile
  • Close follow-up in person or by phone, based on individual need & symptomatology
  • Anti-acid therapy daily as gastric ulcer prevention while on steroids
  • Review steroid medication side effects: mood changes (anger, reactive, hyperaware, euphoric, mania), increased appetite, interrupted sleep, oral thrush, fluid retention
  • Be alert to recurring symptoms as steroids taper down & report them (taper may need to be adjusted)

Long-term high-dose steroids:

  • Consider antimicrobial prophylaxis (sulfamethoxazole/trimethoprim double dose M/W/F; single dose if used daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron®] 1500 mg po daily)
  • Consider additional antiviral and antifungal coverage
  • Avoid alcohol/acetaminophen or other hepatoxins


  • Change in gastrointestinal function, decreased appetite
  • Bloating, nausea
  • More frequent stools, consistency change from loose to liquid
  • Abdominal pain
  • Fever