Objectives: Phenylpropanolamine (PPA) had been used widely as cold remedies or appetite suppressants. However, products containing PPA were withdrawn in sequence in the US, Japan, and Korea due to the increased risk of hemorrhagic stroke. The purpose of this paper was to review safety issues related with the PPA use and hemorrhagic stroke in view of pharmacoepictemiology and pharmacovigilance.
Methods and materials: Researches conducted for evaluating the association between the PPA use and hemorrhagic stroke in other countries were reviewed, which involved case reports, case series, case-control studies, and cohort studies.
Results: In terms of pharmacologic and clinical features, PPA may increase the risk of hemorrhagic stroke through increased blood pressure, heart rate, or vasculitis. The association between the PPA use and hemorrhagic stroke among young women was suggested by case reports from spontaneous adverse events reporting systems or medical journals. The cohort study, using the large prescription database in the US and published in 1984, failed to reveal the association in the population aged below 65. The case-control study conducted as the Yale Hemorrhagic Stroke Project, published in 2000, was the first study to find the association between the PPA as appetite suppressants and hemorrhagic stroke among women ages 18-49 years by well-designed analytic epidemiological research. It led to withdrawal of all products containing PPA in the US and many other countries since 2000. However, the association between PPA and cerebral hemorrhage could not be confirmed by the case-control study conducted in Mexico due to inappropriate recruitment of control group.
Conclusions : During several years case rep0l1s have suggested that hemorrhagic stroke could be induced by PPA, and the Yale Hemorrhagic Stroke Project revealed the association by case-control study and provided a useful model for pharmacovigilance. Nevertheless, their finding could not be applied to other population such as elderly women and male population. And they could not provide any evidence on the association between PPA and stroke when PPA was used as cold remedy taken daily dose below 100mg.
|