Information on QTc-interval prolongation in the summary of product characteristics

Background: The summary of product characteristics (SPC) is the most important source of information for healthcare providers to gain information about the safety of a product, including QTc- related adverse events. However, we have noticed that information regarding QTc prolongation may vary greatly among different products. Objectives: To determine how, and in which sections, QTc-related adverse events are listed in the SPC. Methods: The SPCs of 140 products, centrally approved in Europe between 2006 and 2010, were screened. All products that mentioned the word 'QT' in the SPC were included. We examined in which and in how many different section(s) of the SPC the QTc related adverse event was described. Next we categorized the information on QT prolongation in the warning section (section 4.4) of the SPC to identify inconsistencies in the described information and recorded whether the source of evidence was reported. Results: In total, 22 products were included. The two most common indications were anti-neoplastic drugs (32%) and cardiac therapy (18%). QT related adverse events were most commonly reported in section 4.4 (special warnings and precautions) and section 4.8 (undesirable effects). Six SPCs reported on QT related adverse events in one section (27%), nine in 2 or 3 sections (41%), and seven in 4 or 5 different sections of the SPC (32%). Within section 4.4 the information on QT prolongation varied from 'The ability to cause QT prolongation' (12 SPCs, 55%), to 'explanation of the association of QT prolongation with ventricular arrhythmias' (four SPCs, 18%), 'the advice to act with caution (14 SPCs 64%),or 'the advice to monitor patients using the product' (15 SPCs, 68%). The source of evidence was reported in seven SPCs (32%). Conclusions: These results confirm that information regarding QTc prolongation varies greatly among different products. We advise the development of a guideline concerning reporting on QT prolonging in SPCs, in order to guide prescribers more clearly.