Ibrutinib (Imbruvica®) Management

Written by: Jody Agena, PharmD, MBA, BCOP
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Description: Ibrutinib is a small molecule that acts as a potent, irreversible inhibitor of Bruton’s Tyrosine Kinase (BTK), a key component of the B-cell receptor and cytokine receptor signaling pathway.  BTK inhibition is vital for decreased malignant B-cell proliferation and survival.  This molecule disrupts the proliferation of B-cell cancers such as Mantle Cell Lymphoma (MCL), Chronic/Small Lymphocytic Leukemia (CLL/SLL), Marginal Zone Lymphoma (MZL), Waldenström’s Macroglobulinemia (WM), and chronic Graft Versus Host Disease (cGVHD). Management of both medication dosing and adverse effects are prime examples of key areas for additional intervention opportunities for improved patient health outcomes within the medically integrated team.

Background: Dosing of ibrutinib varies by disease and indication and should therefore be carefully assessed. Lymphocytosis is a noted adverse effect of ibrutinib which results in an increased lymphocytes count. This adverse drug reaction is a common and expected occurrence which is does not reflect progression of the disease. Monitoring patient laboratory values must be considered and evaluated based on patient-specific need.

PQI Process: Upon receiving new ibrutinib prescription:

  • Confirm appropriate indication and dosing
  • Monitor CBC at baseline, monthly and as clinically necessary
  • Monitor CMP, uric acid levels at baseline, monthly and as clinically necessary
  • ECG at baseline (patients with a positive cardiac history/risk factors) and periodically as clinically necessary
  • Evaluate patients on anticoagulation, including low-dose aspirin, for bleeding risk. The use of anticoagulation with ibrutinib should be assessed with each patient based on risk versus benefit. It is recommended to withhold ibrutinib 3 days pre/post minor surgical procedures and pre/post 7 days for major surgical procedures
  • Consider Pneumocystis Jirovecii Pneumonia (PJP) prophylaxis in patients with increased risk of opportunistic infections
  • Upon initiation of ibrutinib, lymphocytosis commonly occurs in first weeks and resolves by week 8 (median) of therapy *Does not reflect disease progression*
  • Monitor adherence and compliance

Dosing Guidelines


Dose (Daily)


420 mg

Mantle Cell Lymphoma

560 mg

Marginal Zone Lymphoma

560 mg

Waldenstroms Macroglobulinemia

420 mg


420 mg

 Adverse Effects

Adverse Reaction

Grade ≥3 (%)







Cardiac Arrhythmia





Adverse Reaction

All Grades (%)





Musculoskeletal Pain


Peripheral Edema


Upper Respiratory Tract Infection






Secondary Malignancies



Recommended Dose Modifications for Toxicity Occurrences

Toxicity Occurrence

MCL and MZL After Recovery Starting Dose = 560 mg

CLL/SLL, WM, and cGVHD After Recovery Starting Dose = 420 mg


Restart at 560 mg daily

Restart at 420 mg daily


Restart at 420 mg daily

Restart at 280 mg daily


Restart at 280 mg daily

Restart at 140 mg daily





Drug Interactions:

  • CYP3A4 Inducers (Strong): May decrease the serum concentration of ibrutinib. (ex. carbamazepine, rifampin, phenytoin, St. John’s Wort)Risk: Avoid combination
  • CYP3A4 Inhibitors (Strong): May increase the serum concentration of ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (ex. anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued (ex. ketoconozole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin). Risk: Avoid combination
  • Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of vaccines. Immunosuppressants may diminish the therapeutic effect of vaccines. Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.Risk: Avoid combination
  • Warfarin and anticoagulation: Increased bleeding risk: Consider risk versus benefit
    • Secondary analysis of RESONATE trial and Phase I study participants on anticoagulation and ibrutinib showed that among 175 patients receiving concomitant anticoagulant or antiplatelet agents, 5 had major bleeding events (3%), and Grade 1 bleed in occurred in 10-20%. These events were typically observed in conjunction with other factors, such as coexisting medical conditions and/or concurrent medications6

Patient Centered Activities:

  • Provide Oncology Chemotherapy Education (OCE) sheet
  • Ensure patients understand the formulation prescribed and how to take their dose
    • Varying dosage forms: capsules – 70 mg, 140 mg; tablets – 140 mg, 280 mg, 420 mg, 560 mg
  • Administer orally once daily with a glass of water
  • Swallow whole; do not break, crush, chew
  • If a dose of ibrutinib 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
  • Proper sign/symptom monitoring
    • If any abnormal bruising or bleeding especially those on anticoagulation or aspirin
    • If there are any new medications (assess for risk of QT prolongation or drug-drug interactions)
    • Evaluate if patients have missed any doses between cycles to determine if interventions are needed such as reminders, calendars, pill boxes, etc


  1. Dimopoulos MA, Tedeschi A, Trotman J, et al; iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia. Phase 3 trial of ibrutinib plus rituximab in Waldenström’s macroglobulinemia. N Engl J Med. 2018;378(25):2399-2410
  2. Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223
  3. Noy A, de Vos S, Thieblemont C, et al. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017;129(16):2224-2232
  4. Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015;126(6):739-745
  5. Miklos D, Cutler CS, Arora M, et al. Multicenter open-label phase 2 study of ibrutinib in chronic graft versus host disease (cGVHD) after failure of corticosteroids. Blood. 2016;128(22)
  6. Jones JA, Hillmen P, Coutre S, et al. Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib. Br J Haematol. 2017;178(2):286-291.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.

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