Abstract 1623P
Background
Anticancer treatments has been changing over the years, evolving from chemotherapy (platinum salts) to targeted therapies, including Tyrosine Kinase Inhibitors (TKI). Because this class of drugs is extensively used, drug–drug interactions (DDI) are an increasing risk in clinical practice. The aim of this work was to check all the TKI’s SmPCs (Summary of Product Characteristics) and the international literature for potential DDI.
Methods
All SmPCs of TKI indicated were checked on the EMA website as well as the international literature. All the main potential pharmacological characteristics that could include a DDI involving CYP3A4, P-gp, BCRP and plasmatic protein were recorded.
Results
Thirty eight TKIs were identified. Of these, 92.1%, 89.5% and 94.7% were a substrate, an inhibitor and/or an inducer of CYP3A4, P-gp and BCRP respectively. Regarding CYP3A4, 18.4% (7/38) were moderate/strong inhibitor or inducer and 13.2% (5/38) were weak inhibitor of this isoenzyme. Furthermore, 26.3% (10/38) were an inhibitor or an inducer of CYP3A4 without more details about the “power” of inhibition/induction. Of these 38 TKIs, (57.9%) 22/38 were P-gp inhibitors and only one TKI was a P-gp inducer. Furthermore, 39.5% (15/38) were concomitant CYP3A4/P-gp inhibitors and there were no concomitant CYP3A4/P-gp inducer. Regarding BCRP, 63.2% (24/38) of the TKIs were BCRP inhibitors. Finally, 89.5% (34/38) were highly bound to plasma proteins (>90%).
Conclusions
This review of the SmPCs and main pharmacokinetic publications of TKIs reported that many of these drugs are potentially exposing patients to DDI with another drug. Consequently, it is important to be aware of this before associating TKIs with another drugs, such as direct oral anticoagulants in cancer associated thrombosis patients, antibiotics or antivirals drugs in case of infection and antiepileptic drugs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
LEO Pharma.
Disclosure
N. Janus: Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Baxter, B-Braun, Daichii-Sankyo, Gilead, Fresenius Medical Care, Leo Pharma, Pfizer, Amgen, Vifor Pharma; Financial Interests, Institutional, Research Grant: Daichii-Sankyo, Gilead, Fresenius Medical Care, Ipsen, Teva, Leo Pharma, Amgen, Roche, Vifor Pharma, Pierre Fabre, Guerbet; Financial Interests, Personal, Full or part-time Employment: Leo Pharma; Financial Interests, Institutional, Invited Speaker: Guerbet.