Background Clinical trial (CT) data have some limitations due to their design: patient recruitment for CTs select patient groups in terms of age, comorbidities and concomitant medication. Real life settings can be different and a specific opportunity for patient intervention may exist in novel drugs. Ibrutinib is the first bruton kinase inhibitor, and is indicated for patients with chronic lymphocytic leukaemia and mantle cell lymphoma. A literature search was performed to assess previous work with this drug.
Purpose To assess opportunities for pharmaceutical intervention based on real life data regarding concomitant medications and reported adverse events (AE) that could lead to dosage adjustments/suspension for patient safety.
Material and methods For every patient that started ibrutinib between January 2015 and August 2016, clinical records were examined for concomitant medications, reported AE, dose adjustments/suspension. Concomitant medication was scanned for potential drug–drug Interactions (DDI).
Results 21 patients initiated ibrutinib. 7 patients suspended therapy, 2 due to disease progression, 1 to unrelated motives and 4 to toxicity. AE: gastrointestinal (33%); haemorrhaging (14%); haematological grade 3–4 (24%); tiredness/pain (19%); respiratory tract infections (57%); non-infectious pneumonitis (9.5%); exacerbated hypertension (9.5%); atrial fibrillation (5%); and dermatologic (5%). Dosage adjustment/suspension of ibrutinib due to AE occurred in 62% of patients. Concomitant medications were present in 95% of patients, 12 had at least a major or moderate DDI with ibrutinib. CYP4503A4 inhibitors, P-gp substrates and drugs increasing ibrutinib’s haemorrhagic potential were involved in interaction mechanisms. Concomitant CYP4503A4 inhibitor usage led to 9 dosage adjustments of ibrutinib and 2 of the CYP4503A4 inhibitor.
Conclusion Rate and type of AE were more serious than reported in CTs. Considering the 57% of patients with significant DDI and 62% with dose adjustments due to AE, it is clear that drug optimisation is relevant for the outcome of the treatment and patient safety. Pharmacists can support this process by reviewing all the medication, monitoring AE, supporting patient compliance and providing feedback to the physicians and/or replacing physician intervention. This review was presented to the haematology department and a systematic pharmaceutical intervention was implemented.
References and/or acknowledgements The Importance of Pharmacovigilance during Ibrutinib Therapy for Chronic Lymphocytic Leukaemia (CLL) in Routine Clinical Practice.
No conflict of interest
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