Adverse Reactions and Diarrhea Management With EXKIVITY (mobocertinib)

Initiating and managing treatment with EXKIVITY

ANTICIPATE¹

Prior to initiation, educate patients on the signs and symptoms of possible side effects—such as diarrhea—and advise patients to report ARs immediately.

ADDRESS¹

Proactively monitor for ARs, and promptly manage with supportive strategies.

MANAGE^1,2

Start EXKIVITY at the recommended dose of 160 mg orally once daily. Dose interruptions and dose reductions may help manage ARs. To potentially optimize outcomes with EXKIVITY, maintain the recommended daily dose of 160 mg whenever appropriate, safe, and tolerated by your patient.

>80%

of adverse reactions did not lead to permanent treatment discontinuation¹

FIND OUT MORE ABOUT DISCONTINUATIONS AND DOSE MODIFICATIONS

“EXKIVITY has an established safety profile. I help my patients start and stay on track with proactive patient counseling and early management of adverse reactions. In particular, I make sure to discuss the potential for diarrhea and rash.¹ By putting a plan in place, my patients are prepared when adverse reactions do arise and are better able to manage these symptoms.”

–Beth Sandy, MSN, CRNP

Abramson Cancer Center, University of Pennsylvania

Help your patients start and stay on track with proactive counseling and early management of adverse reactions (ARs)

Dosing and Patient Management GuideDOWNLOAD GUIDE

EXKIVITY Patient Starter KitORDER A KIT

Note: Request an EXKIVITY Starter kit only if you are using a medically integrated pharmacy. A kit will automatically be sent to patients if you are utilizing Onco360 or Biologics as your specialty pharmacy or if they are enrolled in Takeda Oncology Here2Assist^®.

Monitoring and managing adverse reactions

Expand below to read details on how to monitor and manage select adverse reactions for patients taking EXKIVITY.

Patient monitoring overview¹

Find a summary of monitoring considerations for EXKIVITY (mobocertinib) associated with its Boxed Warning along with the Warnings and Precautions.

EXKIVITY has a Boxed Warning for QTc prolongation and Torsades de Pointes
WARNINGS AND PRECAUTIONS include: QTc prolongation and Torsades de Pointes, ILD/pneumonitis,
cardiac toxicity, diarrhea, and embryo-fetal toxicity

Find a summary of monitoring considerations for EXKIVITY (mobocertinib) associated with its Boxed Warning along with the Warnings and Precautions.

EXKIVITY has a Boxed Warning for QTc prolongation and Torsades de Pointes
WARNINGS AND PRECAUTIONS include: QTc prolongation and Torsades de Pointes, ILD/pneumonitis, cardiac toxicity, diarrhea, and embryo-fetal toxicity

Monitor patients for¹:

QTc and electrolytes at baseline and periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation
New or worsening pulmonary symptoms indicative of ILD/pneumonitis
Changes in cardiac function, including assessment of left ventricular ejection fraction at baseline and during treatment
Signs of diarrhea and changes in electrolytes. Advise patients to start an antidiarrheal agent (e.g., loperamide) at the first sign of diarrhea or increase in bowel movement frequency. Advise patients to increase fluid and electrolyte intake

Based on the safety profile of EXKIVITY observed in the registration study, it is recommended to monitor patients more frequently the first two weeks after initiation of treatment, so any adverse reactions, such as diarrhea, can be addressed promptly. Learn more about AR management below.

QTc interval prolongation¹

Review the EXKIVITY (mobocertinib) Boxed Warning, for QTc prolongation and Torsades de Pointes and learn about patient monitoring and management.

Incidence of QTc interval prolongation

In the 250-patient subset of the pooled EXKIVITY safety population (N=256) who had scheduled and unscheduled electrocardiograms (ECGs), 1.2% of patients had a QTc interval >500 msec and 11% of patients had a change-from-baseline QTc interval >60 msec.

Grade 4 Torsades de Pointes occurred in 1 patient (0.4%)
Clinical trials of EXKIVITY did not enroll patients with baseline QTc greater than 470 msec

Dose modifications and CTCAE definition of QTc interval prolongation by grade

Monitoring¹

Assess QTc interval and electrolytes at baseline and correct abnormalities in sodium, potassium, calcium, and magnesium prior to initiating EXKIVITY
Monitor QTc interval and electrolytes periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc interval prolongation, such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities

Concomitant use with other medications¹

Avoid concomitant use of other medications known to prolong the QTc interval with EXKIVITY, including strong or moderate CYP3A inhibitors
If concomitant use of moderate CYP3A inhibitors cannot be avoided, reduce the EXKIVITY dose by approximately 50% (i.e., from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg) and monitor the QTc interval more frequently. After the moderate CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume EXKIVITY at the dose taken prior to the initiation of the moderate CYP3A inhibitor

Patient counseling information¹

Inform patients of the risk of QTc interval prolongation
Symptoms that may be indicative of significant QTc interval prolongation include:
- Dizziness
- Lightheadedness
- Syncope
Advise patients to report these symptoms and to inform their healthcare provider about the use of any heart medications

Diarrhea¹

Find information on helping patients taking EXKIVITY (mobocertinib) manage diarrhea. It should be treated promptly at the first episode of loose stool with an antidiarrheal such as loperamide along with adequate fluid and electrolyte intake.

In the clinical trial, diarrhea was common, sometimes severe, and transient in many patients. It should be treated promptly with supportive strategies^1,4

Chart showing occurrence of diarrhea in the clinical trial for EXKIVITY.

21% of patients experienced Grade 3 diarrhea; 1% (1 patient) experienced Grade 4⁴
11% of patients required dose reductions and 4% discontinued due to diarrhea⁴

EXKIVITY diarrhea management

ANTICIPATE:

Proactively counsel patients, as diarrhea could occur within 24 hours after administration of EXKIVITY¹

Median time to
ONSET
5 days
but may occur
throughout therapy¹

Median time to
RESOLUTION
3 days
in the 48% of patients
whose diarrhea resolved¹

Instruct patients to have an antidiarrheal (eg, loperamide) readily available to help address first sign of diarrhea or increased bowel movement frequency and to increase fluid and electrolyte intake.¹

ADDRESS:

Treat diarrhea promptly at first episode of loose stool¹

Treat with an antidiarrheal and adequate fluid intake per your clinical practice.¹

If using loperamide as the antidiarrheal treatment, refer to loperamide product labeling for additional information^1,3
Monitor electrolytes and instruct patients to increase fluid and electrolyte intake¹
In the clinical trial, IV hydration was considered for Grade 3 or Grade 4 diarrhea⁴

Dose modifications and CTCAE definition of diarrhea by grade

“I ensure my patients have over-the-counter anti-diarrheal medications on hand when taking EXKIVITY. In my experience, counseling patients on how to manage diarrhea is critical. Oftentimes, we are able to manage their side effects and help patients to stay at the recommended 160 mg dose of EXKIVITY once daily to treat their cancer.”

—Beth Sandy, MSN, CRNP

Abramson Cancer Center, University of Pennsylvania

Request an EXKIVITY Patient Starter Kit with 24 capsules of loperamide for patients to use as needed at the first sign of diarrhea

EXKIVITY Patient
Starter KitORDER A KIT

Patient counseling information¹

Before starting treatment, counsel your patient on the signs and symptoms of diarrhea and the importance of openly and rapidly communicating ARs. Establish baseline bowel movements.

Advise patients:

Diarrhea, which may be severe, occurs commonly during treatment with EXKIVITY^® (mobocertinib) and should be treated promptly
To have antidiarrheal medicine (eg, loperamide) readily available and to promptly start antidiarrheal treatment, increase oral fluids and electrolyte intake, and contact their healthcare provider if diarrhea occurs

Let patients know who they should contact from their healthcare team if they experience symptoms of dehydration, such as lightheadedness, dizziness, or fainting

Consider discussing dietary changes with your patients

Eating simply and staying hydrated can help your patients manage their diarrhea. Consider referring patients to a nutritionist or dietitian for a personalized approach.

Some helpful tips may include:

Consume foods that are high in potassium and sodium (e.g., bananas, apricots, broths, and sports drinks)⁵

Consume more small meals each day instead of 3 large meals⁶

Maintain adequate fluid intake (~8 cups of clear liquid per day), preferably using fluids that help replace lost electrolytes^1,7

Eliminate dairy and foods that are greasy, spicy, or fried, as well as cruciferous vegetables (e.g., broccoli, cabbage, cauliflower)⁸

Stomatitis, vomiting, and nausea¹

Review details on other common EXKIVITY (mobocertinib) GI-related adverse reactions in the clinical trial including stomatitis, vomiting, and nausea.

Counsel on, monitor for, and address other common GI-related ARs to help patients stay on treatment

^*Graded per NCI CTCAE v5.0.

^†Stomatitis includes angular cheilitis, aphthous ulcer, cheilitis, mouth ulceration, mucosal inflammation, odynophagia, and stomatitis.

^‡Events of Grade 3 only (no Grade 4 occurred).

Stomatitis management considerations

Educate patients on dental and oral hygiene. Counsel patients to floss and use a soft-bristle brush, and to rinse with sodium-bicarbonate–based and alcohol-free mouthwash^9,10
Regular mouth rinse can help mitigate symptoms¹¹
Counsel patients to avoid irritating, hot, acidic, or spicy foods and to instead eat soothing food (e.g., mashed potatoes at cold or room temperature)⁹

Nausea and vomiting management considerations

Taking EXKIVITY with a low-fat meal or at a different time of the day may help^2,4,12
Using antiemetics, following the BRAT diet, and eating smaller, more frequent meals may also help⁹

Skin reactions¹

Learn about supportive strategies to help manage skin reactions with EXKIVITY (mobocertinib), such as rash and dry skin, which were generally mild to moderate.

In the clinical trial, skin reactions were common, generally mild to moderate, and managed with supportive strategies^1,4

*Graded per NCI CTCAE v5.0.

^†Rash includes acne, dermatitis, dermatitis acneiform, rash, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, and urticaria.

^‡Events of Grade 3 only (no Grade 4 occurred).

^§Paronychia includes nail bed tenderness, nail disorder, nail infection, onycholysis, and paronychia.

Rash incidence included 19% of patients who experienced acneiform dermatitis (0% Grade 3/4) and 14% who experienced maculopapular rash (2% Grade 3/4)⁴
One patient discontinued treatment due to skin-related ARs⁴

EXKIVITY skin reaction management

ANTICIPATE:

Proactively counsel patients and assess skin toxicities throughout treatment⁴

Median time to
ONSET
9 days

Median time to
RESOLUTION
78 days
(for Grade 3 events: 38 days)

Counsel patients on preventative strategies¹³
Consider dermatology referral for preexisting skin conditions (ie, rosacea, acne, or eczema)¹³

ADDRESS:

Treat skin reactions promptly and continue assessments throughout treatment

Consider the following interventions based on clinical practice:

Topical corticosteroids and/or oral antibiotics to supplement a patient's usual skin care¹⁴
Topical steroids, antimicrobials, and silver nitrate for paronychia^13,15,16

In the clinical trial, the most common treatments for skin-related ARs were corticosteroids (43%), including hydrocortisone (12%), and topical antibiotics (28%), including clindamycin (22%).⁴

For recurrent or persistent skin-related ARs, consider dermatology referral¹⁷

Patient counseling information

Rash and dry skin

Counsel patients on preventative steps and instruct them to communicate side effects promptly. Additionally, please advise patients to:

Minimize sun exposure, apply sunscreen regularly, and wear sun-protective clothing such as wide-brimmed hats and loose-fitting, long-sleeve shirts^18,19
Keep skin soft by using an alcohol- and fragrance-free skin cream^13,19
Avoid hot showers or baths—use lukewarm water instead^13,19
Avoid scratching the skin
Use a gentle cleanser^18,19

Paronychia

Counsel patients on the signs and symptoms of paronychia and communicate preventative measures. Advise patients to^1,13:

Avoid nail trauma such as manicures/pedicures and putting pressure on the nail bed^19,20
Keep affected areas dry and avoid exposure to moisture¹⁹
Wear gloves when washing dishes and using household cleaning products¹⁹
Avoid tight-fitting shoes¹⁹

DISCOVER DOSE MODIFICATIONS
FOR ADVERSE REACTIONS

AR, adverse reaction; ADL, activities of daily living; BRAT, bananas, rice, applesauce, toast; CTCAE, Common Terminology Criteria for Adverse Events; CYP3A, cytochrome p450, family 3, subfamily A; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; GI, gastrointestinal; HCP, healthcare professional; IV, intravenous; N/A, not applicable; NCI, National Cancer Institute; qd, once daily; QTc, corrected QT; TKI, tyrosine kinase inhibitor.

Adverse Reactions and Diarrhea Management With EXKIVITY (mobocertinib)

Help your patients start and stay on track with proactive counseling and early management of adverse reactions (ARs)

Patient monitoring overview1

QTc interval prolongation1

Diarrhea1