Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride.
BACKGROUND
Propranolol hydrochloride, one of the most widely used beta-blocker in the treatment of hypertension since 1960s, shows a number of serious and non-serious adverse events.


OBJECTIVE
Major objectives of this study were to extract the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) database for possible toxic signal detection (SD) of propranolol hydrochloride, evaluate the frequency of the bradycardia associated with it in different stratified groups for a putative signal, and generate awareness in healthcare professionals regarding usefulness of SD.


METHODS
Appropriate statistical methods were used for adverse drug reaction (ADR) signal detection such as, proportional reporting ratio (PRR); reporting odds ratio (ROR); the Chi-square (chi(2)) statistic method; the 95% confidence interval (CI); the observed to expected ratio (O/E); and Du Mouchel method were used to calculate the possible signals. Significance of chi(2) and other calculated statistics, e.g., PRR and ROR, was based on a composite criterion of regulatory guidelines and not on any particular statistical level of significance.


RESULTS
Calculated statistics by different methods were compared with the regulatory criteria of a statistic value >/=4.0 for chi(2), and >/=3.0 for the rest for SD to be declared significant. The PRR statistic was found to be 2.5054; by the ROR method it was 2.5820; the chi(2) statistic was 3.2598, whereas the lower and upper limits of 95% CI of PRR were found to be 0.0778 and 1.9104, respectively, by the O/E ratio was found to be 2.3978, and PRR with the help of Du Mouchel was found to be 2.3979. Thus, the bradycardia-propranolol signals calculated in this study were not significant.


CONCLUSIONS
The therapeutic class specific signal of bradycardia associated with propranolol hydrochloride was not found potent enough to cause bradycardia. However, since the calculated statistics were very high albeit not significant, the possibility of bradycardia-propranolol pairing should still be analyzed from larger databases.
Department of Pharmacology, SPTM Shirpur Campus SVKM's NMIMS University, Mumbai, India.
Dhaval K
DK
Gavali
Kala S
KS
Kulkarni
Amal
A
Kumar
Bhaswat S
BS
Chakraborty