Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 31 (2), 169-80

A Surveillance Method for the Early Identification of Idiosyncratic Adverse Drug Reactions


A Surveillance Method for the Early Identification of Idiosyncratic Adverse Drug Reactions

Fatma A Etwel et al. Drug Saf.


Background: Pemoline is a CNS stimulant that was introduced in 1975 in the US and was used to treat children with attention deficit hyperactivity disorder. Pemoline was withdrawn from the market 30 years later because of fatal hepatotoxicity associated with its use.

Objective: To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle.

Method: All case reports of acute liver failure associated with pemoline and reported to the US FDA from 1975 through 1999 were reviewed. All published articles on pemoline-induced hepatotoxicity were reviewed, and the Naranjo adverse drug reaction probability scale was applied. The incidence rate of idiopathic acute liver failure was estimated from the published literature. The data were analyzed using Fisher's Exact test and relative risks (RR) were calculated.

Results: As early as 1978, there was a significant signal indicating that pemoline was associated with acute liver failure, with an RR of 24.08 (95% CI 4.67, 124.10; p < 0.05). With an increased number of cases, the significance of the association had been steadily increased.

Conclusion: This method enables researchers, clinicians, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier than they currently are in the course of marketing and thus quantify serious adverse events.

Similar articles

See all similar articles

Cited by 5 articles


    1. Drug Saf. 1997 Jun;16(6):355-65 - PubMed
    1. J Sch Health. 1979 Jun;49(6):317-21 - PubMed
    1. J Pediatr Gastroenterol Nutr. 1990 Feb;10 (2):239-41 - PubMed
    1. J Pediatr. 1998 May;132(5):894-7 - PubMed
    1. Practitioner. 1976 Jul;217(1297):61-5 - PubMed

MeSH terms

LinkOut - more resources