Causative drugs for drug-induced cutaneous reactions in central China: a 608-case analysis<sup>,</sup>

Zhao, Jun; Hu, Lei; Zhang, Lihua; Zhou, Maosong; Gao, Lichen; Cheng, Lin

doi:10.1016/j.abd.2019.01.007

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Investigation • An. Bras. Dermatol. 94 (6) • 2019 • https://doi.org/10.1016/j.abd.2019.01.007 copy

Causative drugs for drug-induced cutaneous reactions in central China: a 608-case analysis^☆ ☆ How to cite this article: Zhao J, Hu L, Zhang L, Zhou M, Gao L, Cheng L. Causative drugs for drug-induced cutaneous reactions in central China: a 608-case analysis. An Bras Dermatol. 2019;94:664-70. ^,^☆☆ ☆☆ Study conducted at the Central South University, Changsha, China; Wenzhou Medical University, Wenzhou, China.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

Reports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions.

Objective:

To explore the causative drugs that led to cutaneous reactions.

Methods:

Adverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs.

Results:

The male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n = 482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n = 126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions.

Study limitations:

The small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study.

Conclusions:

Gender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.

KEYWORDS
Drug eruptions; Drug hypersensitivity; Drug-induced cutaneous adverse reactions; Drug-induced severe cutaneous adverse reactions; Pharmacovigilance

Hospital	Time (years)	Cases	Patient type
Wuhan No. 1 Hospital	2010-2011	482	Patients with drug eruption^a a Unknown drugs that induce drug eruption were ruled out. ,^b b Patients intake ≤ 5 total drugs were analyzed.
Xiangya Hospital	2009-2014	126	Patients with severe drug eruption^a a Unknown drugs that induce drug eruption were ruled out. ,^b b Patients intake ≤ 5 total drugs were analyzed.

Group	Ranking	Causative drugs	ATC codes	Cases	% vs. subtotal	% vs. total
Single-medicine use	1	Antibiotics	A07AA, C05AB, D01AA, D06A, D06AX, G01AA, J02AA, J04AB, R02AB, R02AB	201	48%
	2	Herbs and Chinese medicine	-	66	16%
	3	Allopurinol	M04AA01	38	9%
	4	NSAIDs	M01A, M01AX, S01BC	30	7%
	5	Sedative-hypnotics and antiepileptics	N05C and N03	20	5%
	6	Nitroimidazole	P01AB, P01CA	12	3%
	7	Antihypertensives and lipid modifying agents	C02 and C10	12	3%
	8	Serum and vaccine	G03GA03, J06AA03, J06AA06 and J07	9	2%
	9	Digestive system drugs	A09	5	1%
	10	Biological agents	B05A, L03AB, L03AC, L04AB, etc.	3	1%
	11	Antifungals	D01	3	1%
	12	Antithyroid preparations	H03B	3	1%
	13	Antivirals	S01AD	1	0%
	14	Others^a a Anti-prostatic hyperplasia, pesticides, mango, etc.	-	17	4%
		Subtotal		420		87%
Combined-medicine use	1	Antibiotics + antibiotics	S01AA30	21	34%
	2	Antibiotics + others	S01AA20	17	27%
	3	Antibiotics + nitroimidazole	-	8	13%
	4	Herb + herb	-	3	5%
	5	Antiepileptics + antiepileptics	-	2	3%
	6	Nitroimidazole + nitroimidazole	-	1	2%
	7	Others^b b Serum products, non-steroidal anti-inflammatory drugs (NSAIDs), anti-tumor medicine, herbs, etc.	-	10	16%
		Subtotal		62		13%
Total				482

Drugs	ATC codes	Cases	%
β-lactams	J01C, J01CR, J01D	92	46%
Furan	D08AF, J01XE, P01CC	44	22%
Lincomycin	J01FF02	24	12%
Quinolone	J01M, J01MA, J01MB, S01AE	24	12%
Macrolides	J01FA	8	4%
Sulfonamides	A07AB, C03BA, C03CA, D06BA, G01AE, S01AB	7	3%
Others	-	2	1%
Total		201	100%

SCARs types	Male	Female	Total	%
Severe erythema multiforme	23	25	48	38%
Exanthematous pustulosis	14	19	33	26%
Stevens-Johnsons syndrome	0	4	4	3%
Toxic epidermal necrolysis	2	1	3	2%
Erythroderma	2	0	2	2%
Another severe drug eruption	13	23	36	29%
Total	54	72	126	100%

Groups	Ranking	Causative drugs	ATC codes	Cases	% vs. subtotal	% vs. total
Single-medicine use	1	Sedative-hypnotics and antiepileptics	N05C and N03	18	39%
	2	Antibiotics	A07AA, C05AB, D01AA, D06A, D06AX, G01AA, J02AA, J04AB, R02AB, R02AB	10	22%
	3	Allopurinol	M04AA01	7	15%
	4	Herbs and Chinese medicine	-	5	11%
	5	Nitroimidazole	P01AB, P01CA	2	4%
	6	Dapsone	J04BA02, D10AX05	2	4%
	7	Serum and vaccine	G03GA03, J06AA03, J06AA06 and J07	1	2%
	8	Digestive system medicines	A09	1	2%
		Subtotal		46		37%
Combined- medicine use	1	Two drug combination	-	34	43%
	2	Three drug combination	-	23	29%
	3	Four drug combination	-	14	18%
	4	Five drug combination	-	9	11%
		Subtotal		80		63%
Total				126

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[1] * Corresponding author. E-mail:kjade.cheng@gmail.com (L. Cheng).