Pharmacovigilance during ibrutinib therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in routine clinical practice.
Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A. We evaluated concomitant medication use in 118 ibrutinib-treated CLL patients outside the context of clinical trials. Seventy-five (64%) patients were on medications that could increase ibrutinib toxicity and 4 (3%) were on drugs that could decrease ibrutinib efficacy. Nineteen (16%) patients were on concomitant CYP3A inhibitors (11 moderate, 8 strong), and 4 (3%) were on CYP3A inducers (two patients were on both CYP3A inhibitors and inducers). Although the ibrutinib starting dose was changed in 18 patients on CYP3A interacting medications, no difference in 18-month progression-free survival or rate of ibrutinib discontinuation was observed in patients who were not. In routine clinical practice, 2 of 3 CLL patients commencing ibrutinib are on a concomitant medication with potential to influence ibrutinib metabolism. Formal medication review by a pharmacist should be considered in all patients initiating ibrutinib.
a Department of Pharmacy , Mayo Clinic , Rochester , MN , USA.
Heidi D
HD
Finnes
b Department of Biomedical Statistics and Informatics , Mayo Clinic , Rochester , MN , USA.
Kari G
KG
Chaffee
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Timothy G
TG
Call
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Wei
W
Ding
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Saad S
SS
Kenderian
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Deborah A
DA
Bowen
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Michael
M
Conte
a Department of Pharmacy , Mayo Clinic , Rochester , MN , USA.
Kristen B
KB
McCullough
a Department of Pharmacy , Mayo Clinic , Rochester , MN , USA.
Julianna A
JA
Merten
a Department of Pharmacy , Mayo Clinic , Rochester , MN , USA.
Gabriel T
GT
Bartoo
a Department of Pharmacy , Mayo Clinic , Rochester , MN , USA.
Matthew D
MD
Smith
d Division of Hematology Oncology , Mayo Clinic , Phoenix , AZ , USA.
Jose
J
Leis
e Division of Hematology Oncology, Mayo Clinic , Jacksonville , FL , USA.
Asher
A
Chanan-Khan
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Susan M
SM
Schwager
f Department of Health Sciences Research , Mayo Clinic , Rochester , MN , USA.
Susan L
SL
Slager
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Neil E
NE
Kay
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Tait D
TD
Shanafelt
c Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.
Sameer A
SA
Parikh
D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004347:Drug Interactions; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000071184:Pharmacogenomic Variants; D060735:Pharmacovigilance; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010818:Practice Patterns, Physicians'; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000925:Anticoagulants; D015415:Biomarkers; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D000225:Adenine
Pharmacotherapeutics; chemotherapeutic approaches; prognostication