The Weber-curve pitfall: effects of a forced introduction on reporting rates and reported adverse reaction profiles.
BACKGROUND
In May 1999 Losec MUPS (MUPS) were granted a marketing authorization in the Netherlands, followed by the withdrawal of the Losec capsules (capsules) in September 1999. Both formulations contain omeprazole as active substance. This forced switch resulted in a large number of spontaneous reports of adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb.


METHODS
We calculated and compared the reporting rate of both formulations and grouped the reported adverse reactions into system and organ classes (SOCs) in order to analyse possible differences in the type of reported ADRs.


RESULTS
Lareb received 480 reports on omeprazole formulations between May 1997 and December 2000. A quarter of the reports concerned a decrease in therapeutic effect. The reporting rate on MUPS showed a sharp rise after withdrawal of the capsules, but did not differ significantly from the reporting rate on the capsules. A comparison of the type of reported ADRs showed differences in six SOCs. Elimination of the reports concerning a decreased therapeutic effect reduced the number of different SOC reporting rates. Certain gastrointestinal complaints were reported more frequently as an ADR of MUPS.


CONCLUSIONS
The forced switch caused an increase in reports resembling an early Weber effect rather than a decrease in safety of the newer formulation. However, our analysis cannot exclude differences in pharmacokinetic, pharmacodynamic or safety characteristics.
de Graaf
Linda
L
Netherlands Pharmacovigilance Centre Lareb, Goudsbloemvallei 7, 5237 MH's-Hertogenbosch, The Netherlands. l.degraaf@lareb.nl
Fabius
Mariette A
MA
Diemont
Willem L
WL
van Puijenbroek
Eugène P
EP
D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects; D011358:Product Surveillance, Postmarketing / Q000639:trends
D004791:Enzyme Inhibitors; D009853:Omeprazole