Written by: Derek Gyori, PharmD and Julianne Orr, PharmD
Description: Abemaciclib is FDA-approved in combination with an aromatase inhibitor, fulvestrant, and as a single agent in early high-risk, advanced, or metastatic breast cancer. This PQI will address effective practices for the management of abemaciclib associated diarrhea, a common toxicity with this therapy.
Background: Abemaciclib is an FDA approved Cyclin Dependent Kinase (CDK) 4 and 6 Inhibitor approved for use in hormone receptor (HR) positive and human epidermal growth factor 2 (HER2) negative metastatic breast cancer.1-3 Although the mechanism of abemaciclib-induced diarrhea is not fully understood, management of diet along with drug therapy remains the standard of care in patients with abemaciclib-associated diarrhea. In clinical trials, abemaciclib associated diarrhea most frequently occurred in the first cycle of treatment, with a median onset between 6 and 8 days. Diarrhea was often managed in the clinical trials using anti-diarrheal agents sparing the need for dosage reductions or interruptions in the majority of the population.1,2,3
PQI process: Upon receipt of abemaciclib prescription:
- Screen for appropriate antidiarrheal medication:4,5,6
- Loperamide (OTC)
- Take two caplets (4 mg) followed by one caplet (2 mg) every four hours until diarrhea-free for 12 hours
- Do not exceed 8 caplets (16 mg) per day
- If diarrhea does not improve during the first 24 hours of taking loperamide, the patient should contact their health care provider
- May take up to 12 caplets per day for chemotherapy-induced diarrhea under medical supervision
- May schedule loperamide around the clock before adding another agent
- Diphenoxylate/atropine (Rx)
- Take 2 tablets (5 mg) three to four times daily (max of 8 tablets per day)
- May alternate with loperamide to achieve around the clock coverage
- Common side effects: dry skin and mucous membranes, tachycardia, urinary retention, hyperthermia
- Although uncommon, respiratory depression can occur due to the diphenoxylate
- Tincture of opium (Rx)
- Deodorized tincture of opium 10 mg/mL of morphine – Take 0.6 mL (6 mg) in water every 3- 4 hours
- Common side effects: CNS depression, drowsiness, urinary retention, constipation, nausea, headache
- Although uncommon, respiratory depression can occur
- Loperamide (OTC)
- Follow-up with patient by phone after the first week of therapy
- If severe diarrhea (≥ 7 stools per day), may require inpatient admission for fluid and electrolyte administration
Abemaciclib Dose Modifications
|CTCAE Grade of diarrhea||Abemaciclib dose modification|
|Grade 1||No dose modification required|
|Grade 2||If toxicity dose not resolve within 24 hours to|
≤Grade 1, suspend dose until resolution. No dose
|Grade 2 that persists or recurs after resuming the|
|Suspend dose until toxicity resolves to ≤Grade 1.|
Resume at next lower dose
|Grade 3 or 4 or requires hospitalization||Suspend dose until toxicity resolves to ≤Grade 1.|
Resume at next lower dose
Patient Centered Activities:
- Patient Education
- Provide Oncology Chemotherapy Education (OCE) sheet for abemaciclib and Oncology Chemotherapy Education Supplemental Sheet for diarrhea
- Explain abemaciclib associated diarrhea’s median time to onset in the trials was 6-8 days
- Instruct patient to call their provider at the first sign of diarrhea
- Encourage patients to take loperamide at the onset of a loose, watery stool and every two hours until resolution of diarrhea
- If diarrhea hasn’t improved within 24 hours with treatment, consider reducing dose
- Diet Recommendations:4,5,6
- Avoid greasy, spicy, or fried food
- Avoid milk, caffeine, alcohol, and high fiber vegetables
- Eat small frequent meals
- B.R.A.T Diet – Bananas, Rice, Apple Sauce, Toast
- Drink three or more liters of clear fluid per day
- Water, clear liquids, soup, sports drinks
- Dickler MN, Tolaney SM, Rugo HS et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res 2017; 23(17): 5218-5224.
- Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine J Clin Oncol 2017; 35:2875-2884.
- Goetz, MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017; 35:3638-3646.
- National Comprehensive Cancer Network. Palliative Care (Version 1.2018). https://nccn.org/professionals/physician_gls/pdf/palliative.pdf. Accessed May 16, 2018.
- Rangwala F, Zafar SY, Abernathy AP. Gastrointestinal symptoms in cancer patients with advanced disease: new methodologies, insights, and a proposed approach. Curr Opin Support Palliat Care 2012; 6:69-76.
- Richardson G, Dobish R. Chemotherapy induced diarrhea. J Oncol Pharm Practice 2007; 13:181-198.