Management   |   Patient advice   |   Grading

 

Adverse event management: diarrhoea

Management recommendations1,2

Approach to management depends on which grade is identified in each patient. A breakdown of the management guidelines is displayed below.

 

Grade 1–2:

  • GIOTRIF® (afatinib) treatment is continued at the same dose
  • Patients should be followed closely to avoid dehydration
  • Patients should stop taking laxatives and drink 8–10 glasses of water or clear fluids per day
  • Patients should make dietary changes, as described in the “Advice for Patients” subsection below
  • Start immediately on loperamide. Initially with a dose of 4 mg, then 2 mg after each episode of diarrhoea
    (up to 20 mg/day) until bowel movements cease for 12 hours

 

If Grade 2 diarrhoea persists longer than 48 hours or is intolerable:

  • Continue loperamide treatment
  • Interrupt GIOTRIF® (afatinib) treatment, restarting once diarrhoea symptoms have resolved to Grade ≤1 at a dose reduced by 10 mg to a minimum of 20 mg/day
  • Assess patients for dehydration and electrolyte imbalance and consider intravenous fluids and electrolyte replacement

 

Grade 3–4:

  • Continue loperamide treatment
  • Interrupt GIOTRIF® (afatinib) treatment, restarting once diarrhoea symptoms have resolved to Grade ≤1 at a dose reduced by 10 mg to a minimum of 20 mg/day
  • Admit patient to hospital to monitor progress and to take stool specimen for microbiologic examination
  • Initiate intravenous fluid replacement for ≥24 hours, noting that substantial fluid loss may have occurred
  • Consider prophylactic antibiotics if the patient is neutropenic

 

If diarrhoea symptoms do not resolve to grade ≤1 within 14 days, despite optimal supportive care and treatment interruption:

  • Permanently discontinue GIOTRIF® (afatinib) treatment

Advice for patients1

  • Drink ≥2 L of clear fluids daily to avoid dehydration; some fluids should contain sugar or salt to avoid electrolyte loss
  • Incorporate bananas, rice, apple sauce and toast into their diet (BRAT diet)
  • Avoid food that exacerbates symptoms (e.g. greasy, spicy and fried foods) are difficult to digest or contain lactose/caffeine

Grading3

The diarrhoea grade can be used to guide the management strategy.

Grade 1 

Grade 2

Grade 3

Grade 4

Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline

Increase of 4–6 stools per day over baseline; IV fluids indicated <24hrs; moderate increase in ostomy output compared to baseline; not interfering with ADL

 

Increase of ≥7 stools per day over baseline; incontinence; IV fluids ≥24hrs; hospitalisation; severe increase in ostomy output compared to baseline; interfering with ADL

Life-threatening consequences (e.g. haemodynamic collapse)

Grade 1 

Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline

Grade 2

Increase of 4–6 stools per day over baseline; IV fluids indicated <24hrs; moderate increase in ostomy output compared to baseline; not interfering with ADL

 

Grade 3

Increase of ≥7 stools per day over baseline; incontinence; IV fluids ≥24hrs; hospitalisation; severe increase in ostomy output compared to baseline; interfering with ADL

Grade 4

Life-threatening consequences (e.g. haemodynamic collapse)

 

Adapted from CTCAE version 3.3


ADL=activities of daily living, CTCAE=Common Terminology Criteria for Adverse Events


References

1
Yang JC, et al. Expert Rev Anticancer Ther 2013;13(6):729–736.
2
GIOTRIF® (afatinib) Summary of Product Characteristics, 2018.
3
Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.