TABLE III.

Pharmacologic intervention for diarrhea induced by epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis)²¹, based on ctcae grade

	Grade	Intervention
1	Mild	Stop laxatives. Drink 8–10 glasses of clear fluids daily. Immediately start loperamide: 4 mg (2 tablets) followed by 2 mg (1 tablet) after each loose stool (up to 20 mg daily) until bowel movements cease for 12 hours.
		Maintain dose level of egfr tki.
2	Moderate	See grade 1.
		Continue loperamide. Assess for dehydration and electrolyte imbalance. Consider intravenous fluids and electrolyte replacement.
		If diarrhea does not improve after 48 hours, temporarily discontinue egfr tki. Upon improvement to grade 1, restart egfr tki at a reduced dose (except gefitinib, which should be restarted at the original dose).
3	Severe	See grade 2
		Plus: Use stool cultures to rule out an infectious process. Apply aggressive intravenous fluid replacement for 24 hours or more. Use hospitalization to monitor the patient’s progress. Consider prophylactic antibiotics if the patient is also neutropenic.
		Temporarily discontinue egfr tki. Upon improvement to grade 1, restart egfr tki at a reduced dose (except gefitinib, which should be restarted at the original dose). Permanently discontinue egfr tki if diarrhea does not return to grade 1 within 14 days despite treatment discontinuation and best supportive care.
4	Life-threatening	See grade 3
5	Death

ctcae = Common Terminology Criteria for Adverse Events (version 4.03)²⁷.