JFDA286_proof 14 January 2016 1/6

j o u r n a l o f f o o d a n d d r u g a n a l y s i s x x x ( 2 0 1 6 ) 1 e6

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j o u r n a l h o m e p a g e : w w w.j f d a - o n l i n e . c o m

Original Article

Correlation between drugedrug interactioninduced StevenseJohnson syndrome and related

deaths in Taiwan
Q6

a,*

Fu-Jen Cheng
, Fei-Kai Syu , Kuo-Hsin Lee , Fu-Cheng Chen ,
Chien-Hung Wu a, Chien-Chih Chen a
a Department of Emergency

Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of
Medicine, Kaohsiung County, Taiwan
b
College of Pharmacy, China Medical University, Taichung, Taiwan
c
Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

article info

abstract

Article history:
Received 12 August 2015
Received in revised form

Concomitant use of some drugs can lead to interactions between them resulting in severe

19 October 2015

tionship between drug combinations and SJS-related mortality, with the hope that a

adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome
(SJS) associated with combination drug administration. Therefore, we studied the rela-

Accepted 19 November 2015

retrospective study of this nature would provide information crucial for the prevention of

Available online xxx

future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema

Keywords:
adverse drug reaction
allergy
drug interaction
Stevens-Johnson syndrome
toxic epidermal necrolysis

multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification

695.1) from the National Health Insurance database in Taiwan. Statistical comparisons of
the results were performed using analysis of variance (ANOVA), independent sample ttests, and odds ratio (OR). In this way, the relationship between combinations of SJSinducing drugs and mortality could be determined. A total of 111 patients who had died,
including 63 males and 48 females (66.0 20 and 70.0 17.7 years, respectively), were
suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p 0.049), carbamazepine
and sulfamethoxazole/trimethoprim (TMP) (p < 0.0001), carbamazepine and phenytoin (p <
0.0001), sulfamethoxazole/TMP and phenytoin (p 0.015), sulfadoxine and piroxicam
(p 0.045), phenobarbital and cephalexin (p < 0.0001), ampicillin and erythromycin
(p < 0.0001),

erythromycin and minocycline (p < 0.0001),

and vancomycin and

ethambutol (p < 0.0001) administered 1 month before the patients' deaths. Caution should
be exercised when administering any drugs that may possibly induce SJS. In addition,
attention should be

paid to

ensure prompt identification of

interactions, and patients should

should

be

immediately

be

closely monitored.

possible drug-drug

Furthermore,

medications

dis- continued at the first sign or symptom suggesting the

occurrence of drug-related SJS, and then prompt, adequate supportive care should be
provided.

* Corresponding author. Number 123, Dapi Road, Niaosong Township, Kaohsiung County 833, Taiwan.
E-mail address: a0953283092@yahoo.com.tw (F.-J. Cheng).
http://dx.doi.org/10.1016/j.jfda.2015.11.009
1021-9498/Copyright 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Cheng F-J, et al., Correlation between drugedrug interaction-induced StevenseJohnson syndrome
and related deaths in Taiwan, Journal of Food and Drug Analysis (2016), http://dx.doi.org/10.1016/j.jfda.2015.11.009

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