DOSING & DOSE ADJUSTMENTS FOR DDI
The ONLY BTKi offering once-a-day dosing1
Continue IMBRUVICA® treatment until disease progression or unacceptable toxicity.
Modify dose or avoid IMBRUVICA® use with CYP3A inhibitors and avoid coadministration with strong CYP3A inducers1
See full Prescribing Information for complete dosage and administration details
May be co-administered with proton pump inhibitors2,3
Requires no dose adjustment with acid-reducing agents2,3
Flexibility to start patients at home1*
- No ramp-up dosing needed at therapy initiation
No in-patient monitoring required for administration
Agents administered in combination with IMBRUVICA® require infusion. When administering IMBRUVICA® in combination with rituximab or obinutuzumab, consider administering IMBRUVICA® prior to rituximab or obinutuzumab when given the same day.
- Administer IMBRUVICA® at approximately the same time each day with a glass of water
- Swallow tablets or capsule whole. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets
- If a dose of IMBRUVICA® is not taken at the scheduled time, it can be taken as soon as possible on the same day with a return to the normal schedule the following day. Do not take extra doses of IMBRUVICA® to make up for the missed dose
Once-daily dosing is necessary to ensure inhibition of BTK enzymatic activity1
Inhibition of BTK by IMBRUVICA® has a disruptive effect on 3 key B-cell processes as shown by in vitro and in vivo studies1:
- Inhibits survival and proliferation1,4-8
- Inhibits adhesion1,8-13
- Modulates chemotaxis and trafficking1,7,9,11,13-16
Correlation to clinical effect has not been established.
Discontinuation and dose reduction rates in the CLL/SLL registration studies1
The data below are pooled from 5 randomized controlled clinical trials (RESONATE™, RESONATE™-2, HELIOS, iLLUMINATE™, and E1912) and 1 single-arm, open-label clinical trial (Study 1102) in patients with CLL/SLL (N=2,016 total and n=1,133 patients exposed to IMBRUVICA®)
- 4% to 10% of patients discontinued due to ARs
- ARs leading to discontinuation included pneumonia, hemorrhage, atrial fibrillation, neutropenia, arthralgia, rash, and thrombocytopenia
- Approximately 9% of patients had a dose reduction due to ARs
BTK=Bruton's tyrosine kinase, CLL=chronic lymphocytic leukemia, DDI=drug-drug interaction, SLL=small lymphocytic lymphoma.
- IMBRUVICA® (ibrutinib) Prescribing Information.
- de Jong J, Haddish Berhane N, Hellemans P, Jiao J, Sukbuntherng J, Ouellet D. the pH-altering agency omerprazole affects rate but not the extent of ibrutinib exposure. Cancer Chemoth Pharm. 2018;82:299-308.
- Marostica E, Sukbuntherng J, Loury D, et al. Populations pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemoth Pharm. 2015;75:111-121.
- Burger JA, Buggy JJ. Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013;54(11):2385-2391.
- Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075-13080.
- Cinar M, Hamedani F, Mo Z, et al. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Leuk Res. 2013;37(10):1271-1277.
- Ponader S, Chen S-S, Buggy JJ, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182-1189.
- Herman SEM, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117(23):6287-6296.
- Chang BY, Francesco M, Steggerda S, et al. Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression. Presented at: 104th Annual Meeting of the American Association for Cancer Research; April 6-10, 2013; Washington, DC. Abstract 923.
- Binsky I, Lantner F, Grabovsky V, et al. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. J Immunol. 2010;184(9):4761-4769.
- Kurtova AV, Tamayo AT, Ford RJ, Burger JA. Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. Blood. 2009;113(19):4604-4613.
- Chang BY, Francesco M, de Rooij MFM, et al. Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-2424.
- de Rooij MFM, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590- 2594.
- Kindt TJ, Goldsby RA, Osborne BA. Kuby Immunology. 6th ed. New York, NY: W.H. Freeman; 2007.
- Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood. 2009;114(16):3367-3375.
- Davids MS, Burger JA. Cell trafficking in chronic lymphocytic leukemia. Open J Hematol. 2012;3(S1)-3. Published online February 21, 2012.