GRP-048 Cytotoxic Drugs with the Potential to Prolong the QT Interval
Background Regulation No. 173/CD/8.1.7. from the Portuguese Authority of Medicines and Health Products (INFARMED), issued on 2 August 2012 and titled ‘Ondansetron – dose constraint for injectable drugs’, recommends that ‘care must be taken when administering this antiemetic associated with other drugs that prolong the QT interval, namely several cytotoxic agents’. To effectively implement this recommendation, it was thought advisable to point out, in the computerised hospital drug database, all cytotoxic drugs that prolong the QT interval.
Purpose To review all cytotoxic drugs available in the Portuguese pharmaceutical market to identify those with the potential to prolong the QT interval, in order to allow hospital pharmacists to quickly and efficiently implement the above-mentioned recommendation.
Materials and Methods Literature review based upon all summaries of product characteristics (SPCs) of cytotoxic drugs available in Portugal and 48 literature sources from PubMed, found by intersecting the terms ‘cytotoxic-induced prolongation of the QT interval’, ‘antineoplastic-induced prolongation of the QT interval’ and ‘drug-induced prolongation of the QT interval’ and using the time limit interval from January/2003 to September/2012.
Results A total of 58 cytotoxic agents currently available in Portugal were investigated. Agents with the potential to prolong the QT interval are: arsenic trioxide, capecitabine, dasatinib, doxorubicin, epirubicin, eribulin, gefitinib, lapatinib, nilotinib, sorafenib, sunitinib and vandetanib. Substantial evidence supports the conclusion that arsenic trioxide and vandetanib have a risk of torsades de pointes (TdP) when used as directed in SPC. Regarding eribulin, lapatinib, nilotinib and sunitinib, there is insufficient evidence that they may cause TdP when used as directed in the SPC. Note that the hormone antagonists bicalutamide and tamoxifen also have the potential to prolong the QT interval.
Conclusions The database produced is a valuable tool to Portuguese hospital pharmacists who dispense cytotoxic drugs, contributing to the implementation of one of the recommendations of the above-mentioned regulation.
No conflict of interest.