Dosing modifications for adverse reactions in adults with previously treated cGVHD

Dose modifications for adverse reactions1*

If an adverse reaction listed below occurs, interrupt IMBRUVICA® therapy at each occurrence of the same AR. Once the AR has improved to grade 1 or baseline, follow the recommended dosage modifications below1

Start at approved dose 420 mg

Once daily until disease progression or unacceptable toxicity

ADVERSE REACTION‡§

occurrence

1ST

2ND

3RD

NON-CARDIAC

GRADE 3 or 4: other non-hematological toxicities

Restart at280 mg daily

Restart at140 mg daily

Discontinue

GRADE 3 or 4: neutropenia with infection or fever

Restart at280 mg daily

Restart at140 mg daily

Discontinue

GRADE 4: hematological toxicities

Restart at280 mg daily

Restart at140 mg daily

Discontinue

CARDIAC

GRADE 2: cardiac failure

Restart at280 mg daily

Restart at140 mg daily

Discontinue

GRADE 3: cardiac arrhythmias

Restart at280 mg daily

Discontinue

GRADE 3 or 4: cardiac failure

Discontinue

GRADE 4: cardiac arrhythmias

Discontinue

Please see Section 2 of the Prescribing Information for Dosage and Administration Information for previously treated cGVHD patients age 1 to <12 years.

Certain types and severity of cardiac ARs require discontinuation after first occurrence for only IMBRUVICA®.

For cGVHD, continue IMBRUVICA® until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA® should be discontinued considering the medical assessment of the individual patient.

See full Prescribing Information for Warnings and Precautions.

§Grading based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria, or International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematological toxicities in CLL/SLL.

For Grade 4 non-hematological toxicities, evaluate the benefit-risk before resuming treatment. Excluding cardiac failure and cardiac arrhythmia.

Evaluate the benefit-risk before resuming treatment.

For use with CYP3A inhibitors and inducers, and in patients with hepatic impairment, please see the full Prescribing Information. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.

Abbreviations

AR=adverse reaction, cGVHD=chronic graft versus host disease, CLL=chronic lymphocytic leukemia, CYP3A=cytochrome P450, family 3, subfamily A, iwCLL= International Workshop on Chronic Lymphocytic Leukemia, NCI-CTCAE=National Cancer Institute-Common Terminology Criteria for Adverse Events, SLL=small lymphocytic lymphoma.

Reference

1IMBRUVICA® (ibrutinib) Prescribing Information.