Diarrhea

Patient Evaluation
Patient Counseling
Patient Monitoring
Medical Intervention

Patient Evaluation

Screen for the risk factors of capivasertib-associated diarrhea.

Patient history

Screen patients for a history of diarrhea, concomitant medications, and comorbidities that may increase risk or worsen diarrhea:

Laxatives
Magnesium supplements
GLP-1R
Metformin

Baseline renal function

Perform baseline laboratory evaluation of renal function and electrolytes.

Risk of dehydration

Identify patients who may be at higher risk of developing dehydration.

Patient Counseling

Educate patients on symptoms that require intervention, timely reporting of events, dietary adjustments, and stool monitoring.

Inform patients that the median time to onset of diarrhea is 8 days (range, 2–22 days).

The potential for capivasertib-associated diarrhea and symptoms requiring urgent care

Inform patients about the potential for capivasertib-associated diarrhea and symptoms that may require immediate medical attention. Capivasertib symptoms that may require immediate medical intervention include:

Fever (≥100.5 °F/38 °C)
Severe abdominal cramping
Signs of dehydration

View Incidence

Advise patients to notify the healthcare team when they experience ≥grade 2 diarrhea

Grade 2 diarrhea is defined as an increase of 4–6 stools per day over baseline, or moderate increase in ostomy output, or limiting instrumental activities of daily living (ADL).

Antidiarrheal treatment

Advise patients to have it available before starting capivasertib treatment, and educate patients on the use and escalation of antidiarrheals

Utilizing a stool diary

Encourage patients to utilize a diary to log stool frequency and characteristics, loperamide/antidiarrheal usage, and oral intake.

Capivasertib administration with food

Counsel patients to take capivasertib with food, as this may reduce the incidence of diarrhea.

Diarrhea – incidence

Frequency, time to occurrence, and dose modification of diarrhea under treatment with capivasertib+ fulvestrant in CAPItello-291
¹

1. Iyengar NM, O'Shaughnessy JA, Moore HN, et al. Optimizing clinical monitoring and management guidelines for capivasertib in HR-positive/HER2-negative advanced breast cancer: expert opinion. npj Breast Cancer. 2025;12(1):16. doi:10.1038/s41523-025-00864-2.

	Capivasertib + fulvestrant Overall population (n=355)
Diarrhea of any grade %	72.4
Grade 3*	9.3
Median days to the first occurrence of diarrhea	8 (range 2–22)
Diarrhea leading to dose modification %
Dose interruption	10.0
Dose reduction	8.0
Permanent discontinuation	2.0

Values in the PI may differ slightly from those reported in the Capivasertib Expert Opinion publication due to different cut-off dates and the inclusion of different preferred terms.

*No grade 4 diarrhea ARs were reported.

1. Iyengar NM, O'Shaughnessy JA, Moore HN, et al. Optimizing clinical monitoring and management guidelines for capivasertib in HR-positive/HER2-negative advanced breast cancer: expert opinion. npj Breast Cancer. 2025;12(1):16. doi:10.1038/s41523-025-00864-2.

Patient Monitoring

Encourage patients to maintain a stool diary, bring stool logs to follow-up visits, and contact their HCPs between visits.

Schedule follow-up visits every 2–3 weeks for the first 2–3 months of treatment

Identifying patterns of diarrhea with a diary

Encourage patients to utilize a diary to help with symptom triage and identify whether diarrhea follows a pattern with the capivasertib dosing cycle (4 days on, 3 days off) that can be addressed with prophylactic measures.

Follow-up visits

Advise patients to bring stool logs to follow-up visits with their healthcare team.

Maintain communication

Advise patients to contact their HCPs between visits when needed.

Medical Intervention

Manage diarrhea with a step-wise approach including dietary modifications, antidiarrheal treatments, and capivasertib dose modifications.

Dietary modifications

Recommend the following dietary modifications to patients when they report capivasertib associated diarrhea:

Eating frequent, small meals which may include bananas, applesauce, and toast
Ensuring adequate hydration with clear liquids such as water or broth
Avoiding or limiting high fiber foods such as raw vegetables, beans and whole grains, lactose-containing products, caffeinated and alcoholic beverages, and high-osmolar supplements

Capivasertib dose modifications:

Maintain same dose

PI Recommendation

Antidiarrheal treatments

Initiation:

Loperamide 4 mg followed by 2 mg every 4 hours (maximum, 16 mg/day)

Persistent (>24 hours):

Increase loperamide dose, up to 2 mg every 2 hours (maximum, 16 mg/day)
Consider 1–2 tablets of diphenoxylate 2.5 mg plus atropine 0.025 mg every 6–8 hours in addition or as an alternative to loperamide

Additional HCP intervention

Consider a physical exam, complete blood count, basic metabolic panel including renal function assessment, and testing stool cultures for pathogens.

Test for the following pathogens: Clostridium difficile, Salmonella spp., Campylobacter spp., Giardia spp., Entamoeba spp., Cryptosporidium spp., Shigella spp., and Escherichia coli

Capivasertib dose modifications:

Initial capivasertib dose modification:

Withhold dose until grade ≤1

Dosing at recovery:

Recovery ≤28 days – resume at the same dose or 1 lower dose, as clinically indicated
Recovery >28 days – resume at 1 lower dose
Recurrent grade 2 diarrhea – resume at 1 lower dose

PI Recommendation

Antidiarrheal treatments

Initiation:

Loperamide 4 mg followed by 2 mg every 4 hours (maximum, 16 mg/day)

Persistent (>24 hours):

Increase loperamide dose, up to 2 mg every 2 hours (maximum, 16 mg/day)
Consider 1–2 tablets of diphenoxylate 2.5 mg plus atropine 0.025 mg every 6–8 hours in addition to or as an alternative to loperamide

For severe or persistent diarrhea despite dose interruption and antidiarrheal treatment

Consider a physical exam, complete blood count, basic metabolic panel including renal function assessment, and testing stool cultures for pathogens.

Test for the following pathogens: Clostridium difficile, Salmonella spp., Campylobacter spp., Giardia spp., Entamoeba spp., Cryptosporidium spp., Shigella spp., and Escherichia coli

Capivasertib dose modifications:

Initial capivasertib dose modification:

Withhold dose until grade ≤1

Dosing at recovery:

Recovery ≤28 days – resume at the same dose or 1 lower dose, as clinically indicated
Recovery >28 days – permanently discontinue capivasertib

PI Recommendation

Antidiarrheal treatments

Initiation:

Loperamide 4 mg followed by 2 mg every 2 hours (maximum, 16 mg/day)
Consider 1–2 tablets of diphenoxylate 2.5 mg plus atropine 0.025 mg every 6–8 hours in addition to or as an alternative to loperamide

Persistent (>24 hours):

Discontinue loperamide and/or diphenoxylate plus atropine
Initiate octreotide 100–150 μg SC TID with dose escalation to 500 μg SC TID or tincture of opium

For severe or persistent diarrhea despite dose interruption and antidiarrheal treatment

Consider hospital admission for supportive care with IV hydration, electrolyte repletion, antibiotics, and multidisciplinary care.

Perform complete blood count, basic metabolic panel including renal function assessment, and testing stool cultures for pathogens.

Test for the following pathogens: Clostridium difficile, Salmonella spp., Campylobacter spp., Giardia spp., Entamoeba spp., Cryptosporidium spp., Shigella spp., and Escherichia coli

Consider colonoscopy and imaging in patients with lobular BC to assess for bowel infiltration. This may mimic or exacerbate treatment-related diarrhea and require tailored oncologic management.

Capivasertib dose modifications:

Permanently discontinue capivasertib

PI Recommendation

Antidiarrheal treatments

Initiation:

Loperamide 4 mg followed by 2 mg every 2 hours (maximum, 16 mg/day)
Consider 1–2 tablets of diphenoxylate 2.5 mg plus atropine 0.025 mg every 6–8 hours in addition to or as an alternative to loperamide

Persistent (>24 hours):

Discontinue loperamide and/or diphenoxylate plus atropine
Initiate octreotide 100–150 μg SC TID with dose escalation to 500 μg SC TID or tincture of opium

For severe or persistent diarrhea despite dose interruption and antidiarrheal treatment

Consider hospital admission for supportive care with IV hydration, electrolyte repletion, antibiotics, and multidisciplinary care.

Perform complete blood count, basic metabolic panel including renal function assessment, and testing stool cultures for pathogens.

Test for the following pathogens: Clostridium difficile, Salmonella spp., Campylobacter spp., Giardia spp., Entamoeba spp., Cryptosporidium spp., Shigella spp., and Escherichia coli

Consider colonoscopy and imaging in patients with lobular BC to assess for bowel infiltration. This may mimic or exacerbate treatment-related diarrhea and require tailored oncologic management.

Management upon resolution of diarrhea

Continue dietary modifications and gradually add solid foods. Discontinue loperamide and/or diphenoxylate plus atropine after a 12-hour diarrhea-free interval. For patients requiring multiple medications, consider a gradual taper.Discontinue If resuming capivasertib at the same dose, consider scheduling loperamide (i.e. daily, or based on pattern within capivasertib dosing cycle) to prevent recurrence, then de-escalate as diarrhea improves over time.

Important Safety Information

TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components.

Hyperglycemia

TRUQAP can cause severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes.

Increased fasting glucose (FG) from baseline occurred in 37% of patients treated with TRUQAP, including 11% of patients with Grade 2 (FG >160 to 250 mg/dL), 2% with Grade 3 (FG >250 to 500 mg/dL), and 1.1% with Grade 4 (FG >500 mg/dL) events. The median time to first occurrence of hyperglycemia was 15 days (range: 1 to 367). Dose reduction for hyperglycemia was required in 0.6% of patients and permanent discontinuation was required in 0.6% of patients. Diabetic metabolic decompensation occurred in 0.6% of patients, including diabetic ketoacidosis in 0.3%.

In CAPItello-291, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication either initiated or changed during the study, including treatment with insulin in 4.8% (17/355) of patients.

The safety of TRUQAP has not been established in patients with Type 1 diabetes or Type 2 diabetes that is uncontrolled or requiring insulin at baseline as these patients were excluded from clinical studies. Before initiating treatment with TRUQAP, test fasting glucose levels (fasting plasma glucose or fasting blood glucose), hemoglobin A1C (HbA1C) levels, and optimize fasting glucose. After initiating treatment with TRUQAP, monitor or self-monitor FG levels on Day 3 or 4 of the dosing week during weeks 1, 2, 4, 6, and 8; then monthly while on treatment with TRUQAP; and as clinically indicated. Monitor HbA1C levels every 3 months during treatment with TRUQAP and as clinically indicated. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of FG levels.

For patients who experience hyperglycemia during treatment with TRUQAP, monitor FG at least twice weekly, on days on and off TRUQAP, until FG decreases to baseline levels. During treatment with anti-diabetic medications, monitor FG at least once a week for 2 months, followed by once every 2 weeks, or as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and initiation of FG monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients on the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes.

Withhold TRUQAP immediately when ketoacidosis is suspected. If ketoacidosis is confirmed, permanently discontinue TRUQAP. Withhold TRUQAP in clinical situations known to increase the risk of severe hyperglycemia or ketoacidosis (eg, suspected serious infection or acute illness). Based on the severity of hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP.

Diarrhea

TRUQAP can cause severe diarrhea associated with dehydration.

Diarrhea occurred in 72% of patients. Grade 3 or 4 diarrhea occurred in 9% of patients. The median time to first occurrence was 8 days (range: 1 to 519). In the 257 patients with diarrhea, 59% required antidiarrheal medications to manage symptoms. Dose reductions were required in 8% of patients and 2% of patients permanently discontinued TRUQAP due to diarrhea. In patients with Grade ≥2 diarrhea (n=93) with at least 1 grade improvement (n=89), median time to improvement from the first event was 4 days (range: 1 to 154).

Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity.

Cutaneous Adverse Reactions

TRUQAP can cause cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia (PPE), and drug reaction with eosinophilia and systemic symptoms (DRESS).

Cutaneous adverse reactions occurred in 58% of patients. Grade 3 or 4 cutaneous adverse reactions occurred in 17% of patients receiving TRUQAP. EM occurred in 1.7% of patients and DRESS occurred in 0.3% of patients. Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions.

Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, dose reduce, or permanently discontinue TRUQAP based on severity.

Embryo-Fetal Toxicity

Based on findings from animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose.

TRUQAP is used in combination with fulvestrant. Refer to the full Prescribing Information of fulvestrant for pregnancy and contraception information.

Among the 355 patients who received TRUQAP in CAPItello-291, the most common (≥20%) adverse reactions, including laboratory abnormalities, were diarrhea (72%), cutaneous adverse reactions (58%), increased random glucose (57%), decreased lymphocytes (47%), decreased hemoglobin (45%), increased fasting glucose (37%), nausea and fatigue (35% each), decreased leukocytes (32%), increased triglycerides (27%), decreased neutrophils (23%), increased creatinine (22%), vomiting (21%), and stomatitis (20%).

In the 155 patients with PIK3CA/AKT1/PTEN alterations treated with TRUQAP + fulvestrant, dose reductions due to adverse reactions were reported in 21% of patients. Permanent TRUQAP discontinuation due to an adverse reaction occurred in 10% of patients. Dose interruptions of TRUQAP occurred in 39% of patients.

Strong CYP3A Inhibitors: Avoid concomitant use with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the dose of TRUQAP and monitor patients for adverse reactions.

Moderate CYP3A Inhibitors: When concomitantly used with a moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions.

Strong or Moderate CYP3A Inducers: Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers.

TRUQAP in combination with fulvestrant is indicated for the treatment of adult patients with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alteration as detected by an FDA-authorized test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.

Please see full Prescribing Information, including Patient Information for TRUQAP.

You may report side effects related to AstraZeneca products

ADL	activities of daily living
AE	adverse event
AKT1/2/3	serine/threonine protein kinase 1/2/3
BID	twice daily
BMI	body mass index
BSA	body surface area
CYP3A	cytochrome P450, family 3, subfamily A
DKA	diabetic ketoacidosis
DRESS	drug reaction with eosinophilia and systemic symptoms
eGFR	estimated glomerular filtration rate
EM	erythema multiforme
ET	endocrine therapy
FDA	US Food and Drug Administration
FG	fasting glucose
GI	gastrointestinal

GLP-1R	glucagon-like peptide-1 receptor
HbA1c	hemoglobin A1C
HCP	healthcare professional
IV	intravenous
mBC	metastatic breast cancer
PI3K	phosphoinositide 3-kinase
PIK3CA	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
PTEN	phosphatase and tensin homolog
QD	once daily
SGLT2i	sodium-glucose co-transporter-2 inhibitor
spp	species
T2D	type 2 diabetes
TID	three times daily
TZD	thiazolidinedione
ULN	upper limit of normal

2. TRUQAP. Prescribing information.

3. Rugo HS, Oliveira M, Howell SJ, et al. Capivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 study. ESMO Open. 2024;9(9):103697. doi:10.1016/j.esmoop.2024.103697.

Diarrhea

Summary PDF:

Patient Evaluation

Patient history

Baseline renal function

Risk of dehydration

Important Safety Information

IMPORTANT SAFETY INFORMATION ABOUT TRUQAP® (capivasertib) tablets

ADVERSE REACTIONS

DRUG INTERACTIONS

INDICATION AND USAGE

Abbreviations

References