ADDITIONAL DOSING INFORMATION FOR ADULTS WITH PREVIOUSLY TREATED cGVHD

CYP3A inhibitors and inducers1,2

IMBRUVICA® dose modifications for CYP3A inhibitors in adults with cGVHD*

Coadministered DrugRecommended IMBRUVICA® Dose
Moderate CYP3A inhibitor

420 mg once daily

Modify dose as recommended per Section 2.2 of the full Prescribing Information

Voriconazole 200 mg twice daily

Posaconazole suspension 100 mg once daily, 100 mg twice daily, or 200 mg twice daily

280 mg once daily

Modify dose as recommended per Section 2.2 of the full Prescribing Information

Posaconazole suspension 200 mg three times daily or 400 mg twice daily

Posaconazole intravenously 300 mg once daily

Posaconazole delayed-release tablets 300 mg once daily

140 mg once daily

Interrupt dose as recommended per Section 2.2 of the full Prescribing Information

Other strong CYP3A inhibitors

Avoid concomitant use. If these inhibitors will be used short-term (such as anti-infectives for 7 days or less), interrupt IMBRUVICA®

*Please note that dose modifications for use with CYP3A inhibitors for patients with cGVHD differ from those with B-cell malignancies.

After discontinuation of a CYP3A inhibitor, resume previous dose of IMBRUVICA® per Sections 2.1 and 7.1 of full Prescribing Information.1

  • Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A1

CYP3A Inducers

The coadministration of IMBRUVICA® with strong CYP3A inducers may decrease ibrutinib concentrations. Avoid coadministration with strong CYP3A inducers.

Examples of moderate CYP3A inhibitors include: aprepitant, ciprofloxacin, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, grapefruit juice, imatinib, isavuconazole, tofisopam, verapamil.

Examples of strong CYP3A inhibitors include: cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir and ombitasvir (and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, telithromycin, troleandomycin, voriconazole.

§Examples of strong CYP3A inducers include: apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor, mitotane, phenytoin, rifampin, St. John’s wort. Please note that the induction potency of St. John’s wort may vary widely based on preparation.

These examples are a guide and not considered a comprehensive list of all possible drugs that may fit these categories.

Abbreviations

cGVHD=chronic graft versus host disease, CYP3A=cytochrome P450, family 3, subfamily A.

Hepatic impairment1

The recommended dose is:

  • 140 mg daily for patients 12 years of age and older with total bilirubin level >1.5 to 3 x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome).
  • 80 mg/m2 daily for patients 1 to less than 12 years of age with total bilirubin level >1.5 to 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome).

Avoid the use of IMBRUVICA® in these patients with total bilirubin level >3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome).

Abbreviations

cGVHD=chronic graft versus host disease, ULN=upper limit of normal.

Hemorrhage1

Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms of bleeding.

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 the risk of bleeding.

Abbreviations

cGVHD=chronic graft versus host disease, CYP3A=cytochrome P450, family 3, subfamily A.

References

1IMBRUVICA® (ibrutinib) Prescribing Information. 2US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed January 23, 2023.