Additional Dosing Information for Previously Treated cGVHD
CYP3A inhibitors and inducers1,2
IMBRUVICA® Dose Modifications for CYP3A Inhibitors in cGVHD*
| Coadministered Drug | Recommended 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 seven days or less), interrupt IMBRUVICA® |
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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 Inducers1§
The coadministration of IMBRUVICA® with strong CYP3A inducers may decrease ibrutinib concentrations. Avoid coadministration with strong CYP3A inducers.
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Examples of moderate CYP3A inhibitors include: aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, and verapamil.
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Examples of strong CYP3A inhibitors include: boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, and troleandomycin.
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Examples of strong CYP3A inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and 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.
cGVHD=chronic graft versus host disease, CYP3A=cytochrome P450, family 3, subfamily A.
Hepatic impairment1
The recommended dose is:
- 140 mg daily for patients with mild hepatic impairment (Child-Pugh class A)
- 70 mg daily for patients with moderate hepatic impairment (Child-Pugh class B)
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For patients with mild or moderate hepatic impairment, monitor more frequently for adverse reactions of IMBRUVICA®
Avoid the use of IMBRUVICA® in patients with severe hepatic impairment (Child-Pugh class C).
cGVHD=chronic graft versus host disease.
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.
cGVHD=chronic graft versus host disease, CYP3A=cytochrome P450, family 3, subfamily A.
References:
- IMBRUVICA® (ibrutinib) Prescribing Information.
- US 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 May 23, 2019.