Studies on the Association between Phenylpropanolamine (PPA) and Hemorrhagic Stroke in Other Countries.

Objectives : Phenylpropanulamine (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 However,products containing PPA were withdrawn in sequence in the US, Japan, and Korea due to the increased risk of hemorrhagicstroke. The purpose of this paper was to review safety issues related with the PPA use and hemorrhagic stroke in view ofpharmacoepidemiology and pharmacovigilanceMethods and materials : Researches conducted for evaluating the association between the PPA use and hemorrhagicstroke in other countries were reviewed, which involved case reports, case series, casc-control studies, and cohort studies.Results : in terms of pharmacologic and clinical features, PPA may increase the risk of hemorrhagic stroke throughincreased blood pressure, heart rate, or vasculitis, Thc association between the PPA use and hemorrhagic stroke amongyoung women was suggested by case reports from spontaneous adverse events repoiting systems or medical journals. Thecohort study, using the large prescription database in the US and published in 1984, failed to reveal the association in thepopulation aged below 65, The case-cuntrol study conducted as the Yalc Hemorrhagic Stroke Project, Published in 2000,was the first study to find the association between the PPA as appetite suppressants and hemorrhagic stroke among womenages 18-49 years by well-designed analytic epidemiological research, it led to withdrawal of all products containing PPA inthe US and many other countries since 2000. However, the association between PPA and cerebral hemorrhage could not beconfirmed by the case-control study conducted in Mesxico due to inappropriate recruitment of control group.Conclusions : During -several years case reports have suggested that hcmorrhagic stroke could be induced by PPA, andthe Yale Hemorrhagic Strokc Project revealed the association by case-control study and provided a useful model forphamiacovigilancc. Nevertheless, their finding could not be applied to other population such as elderly women and malepopulation. And They could not provide any evidence on the association between PPA and stroke when PPA was used ascold remedy taken daily dose below 100mg.