Signalling possible drug-drug interactions in a spontaneous reporting system: delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole.
OBJECTIVE
In spontaneous adverse drug reaction reporting systems, there is a growing need for methods facilitating the automated detection of signals concerning possible adverse drug reactions. In addition, special attention is needed for the detection of adverse drug reactions resulting from possible drug-drug interactions. We describe a method for detecting possible drug-drug interactions using logistic regression analysis to calculate ADR reporting odds ratios.


METHODS
To illustrate this method, we analysed the adverse drug reaction 'delayed withdrawal bleeding' resulting from a possible interaction between itraconazole and oral contraceptives in reports received by the Netherlands Pharmacovigilance Foundation LAREB between 1991 and 1998.


RESULTS
In total 5,503 reports were included in the study. The odds ratio, adjusted for year of reporting, age and source of the reports, for a delayed withdrawal bleeding in women who used both drugs concomitantly compared with women who used neither oral contraceptives, nor itraconazole, was 85 (95% CI: 32-230).


CONCLUSIONS
Since spontaneous reporting systems can only generate signals concerning possible relationships, this association needs to be analysed by other methods in more detail in order to determine the real strength of the relationship. This approach might be a promising tool for the development of procedures for automated detection of possible drug-drug interactions in spontaneous reporting systems.
Van Puijenbroek
E P
EP
Netherlands Pharmacovigilance Foundation LAREB, 's-Hertogenbosch, the Netherlands.
Egberts
A C
AC
Meyboom
R H
RH
Leufkens
H G
HG
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D003276:Contraceptives, Oral / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000009:adverse effects*; D008599:Menstruation Disturbances / Q000139:chemically induced*; D008875:Middle Aged; D012044:Regression Analysis
D003276:Contraceptives, Oral; D017964:Itraconazole