Label Changes Related to the QTc Interval

By Bob Roth

In a recent FDA Drug Safety Communication, the Agency announced that the Celexa (citalopram hydrobromide) label now has revised dosing recommendations based on evaluations of post-marketing reports related to QTc prolongation and thorough QTC studies.  The label reasonably stresses the importance of routine ECG monitoring and provides an upper level of prolongation that would necessitate discontinuation of the drug due to cardiac risk of arrhythmia.

In our opinion, somewhat lost in all the good intention is the notion that measurement of QTc,  and identification of prolongation that rises to the level of requiring action, is not all that simple.  Big pharma, in support of clinical trials, may send out ECGs to accredited cardiovascular consultants and specialist CROs for evaluation, programs that have high level training and quality control programs; this is not always the case for a typical general practitioner.   Numerous known confounding  variables (Barbey JT. 2012. Clin Pharm Therapeut 91:580) and technical issues related to measurement of the QTc can introduce considerable uncertainty in the final result.

Drug treatment decisions, based on label-designated blood test abnormalities, are generally supported by the high quality of accredited diagnostics laboratories.  Similarly, required genomics screening for selection of candidate patients, now a common component of many approved drug labels, by default takes place in qualified settings outside the doctor’s office.   We wonder if FDA’s appropriate focus on drug risks of arrhythmia may not be fully addressing the problems inherent in the way in which patients at risk are now being identified.   Specifically, FDA may not fully be taking into account the extent to which the benefit of a medically appropriate decision may be counterbalanced by erroneous data driving that decision.

Bob Roth is Vice President and Worldwide Medical Director at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please contact us.