Objective  To mine the adverse drug event (ADE) signals of minocycline, to provide a reference for clinical drug safety.

Methods  The reporting odds ratio (ROR) method, proportional report ratio (PRR) method, the Medicines and Healthcare Products Regulatory Agency (MHRA) method, and Bayesian confidence propagation neural network (BCPNN) method were used to analyze the ADE reports of minocycline based on U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) registration data from first quarter 2004 to fourth quarter 2023, and the signal distribution, signal intensity, gender and age differences, and mortality based on standard MedDRA query (SMQ) were analyzed.

Results  A total of 16 871 ADE cases of minocycline were screened, and 364 positive ADE signals were mapped to 27 system organ classification (SOC), the most involved SOC were systemic diseases and various reactions at the administration site, skin and subcutaneous tissue diseases, various neurological diseases, etc, and the strong signals with the higher number of ADE cases were drug reaction with eosinophilia and systemic symptoms (DRESS), polyarteritis nodosa and idiopathic intracranial hypertension, and compared to other drugs, the proportion of women with idiopathic intracranial hypertension caused by minocycline was higher (P < 0.05). At the same time, 29 cases of ADE in children under 8 years old were obtained, involving 10 SOC, 206 deaths and 1 046 associated ADE-related cases, and there were 1 565 cases of hypersensitivity ADE, and 88 PT signals under the hypersensitivity SMQ. Among them, DRESS, urticaria, anti-neutral cytoplasm antibody-positive vasculitis, and facial edema were reported in high numbers and with strong signals.

Conclusion  The risk of hypersensitivity events and autoimmune diseases should be vigilant in the clinical use of minocycline, and ophthalmic monitoring could be performed especially in female patients if necessary. Attention should be paid to ADE collection and monitoring of minocycline in children under 8 years old.

1.Fragkou PC, Poulakou G, Blizou A, et al. The role of minocycline in the treatment of nosocomial infections caused by multidrug,extensively drug and pandrug resistant Acinetobacter baumannii: a systematic review of clinical evidence[J]. Microorganisms, 2019, 7(6): 159. DOI: 10.3390/microorganisms7060159.

2.Cunha BA, Baron J, Cunha CB. Similarities and differences between doxycycline and minocycline: clinical and antimicrobial stewardship considerations[J]. Eur J Clin Microbiol Infect Dis, 2018, 37(1): 15-20. DOI: 10.1007/s10096-017-3081-x.

3.慕红文, 陈永强, 王文兴, 等. 米诺环素治疗牙周炎的策略及进展[J]. 药品评价, 2018, 15(8): 27-30. [Mu HW, Chen YQ, Wang WX, et al. Strategy and progress of minocycline in the treatment of periodontitis[J]. Drug Evaluation, 2018, 15(8): 27-30.] DOI: 10.3969/j.issn.1672-2809.2018.08.005.

4.国家卫生健康委员会. 儿童肺炎支原体肺炎诊疗指南（2023年版）[J]. 国际流行病学传染病学杂志, 2023, 50(2): 79-85. DOI: 10.3760/cma.j.cn331340-20230217-00023.

5.Dominic MR. Adverse reactions induced by minocycline: a review of literature[J]. Curr Drug Saf, 2021, 16(3): 309-321. DOI: 10.2174/1574886316666210120090446.

6.刘艳鑫, 董长江, 邹剑, 等. 基于FAERS数据库的替扎尼定不良事件信号挖掘研究[J]. 药物流行病学杂志, 2024, 33(2): 166-175. [Liu YX, Dong CJ, Zou J, et al. Research on signal mining of adverse events of tizanidine based on FAERS database[J]. Chinese Journal of Pharmacoepidemiology, 2024, 33(2): 166-175.] DOI: 10.12173/j.issn.1005-0698.202312038.

7.曾露, 王璐, 魏安华. 基于美国FAERS数据库的达比加群酯不良反应信号挖掘研究[J]. 药品评价, 2023, 20(5): 607-611. [Zeng L,Wang L,Wei AH.Data-mining of adverse drug reaction signals of dabigatran etexilate based on US FAERS[J]. Drug Evaluation, 2023, 20(5): 607-611.] DOI: 10.19939/j.cnki.1672-2809.2023.05.22.

8.刘艳鑫, 邹剑, 董长江, 等. 基于FAERS的胰高血糖素样肽-1受体激动剂不良事件信号挖掘[J]. 医药导报, 2022, 41(7): 975-982. [Liu YX, Zou J, Dong CJ, et al.Research on signal mining of adverse events of GLP-1 receptor agonists based on FAERS[J]. Herald of Medicine, 2022, 41(7): 975-982.] DOI: 10.3870/j.issn.1004-0781.2022.07.009.

9.魏安华, 曾露, 王璐, 等. 基于FAERS 数据库的替诺福韦二吡呋酯和丙酚替诺福韦不良事件分析及肾脏安全性比较[J]. 药物流行病学杂志, 2023, 32(12): 1362-1370. [Wei AH, Zeng L,Wang L, et al. Adverse event analysis and renal safety comparison of tenofovir disoproxiland tenofovir alafenamide based on FAERS database[J]. Chinese Journal of Pharmacoepidemiology, 2023, 32(12): 1362-1370.] DOI: 10.19960/j.issn.1005- 0698.202312006.

10.Lebrun-Vignes B, Kreft-Jais C, Castot A, et al. Comparative analysis of adverse drug reactions to tetracyclines: results of a French national survey and review of the literature[J]. Br J Dermatol, 2012, 166(6): 1333-1341. DOI: 10.1111/j.1365-2133.2012.10845.x.

11.Zhao R, Pedersen EA, Mancuso JB. Minocycline induced drug rash with eosinophilia and systemic symptoms complicated by hemophagocytic lymphohistiocytosis[J]. JAAD Case Rep, 2022, 32: 99-101. DOI: 10.1016/j.jdcr. 2022.11.006.

12.卢翠翠, 李伟哲, 沈姗, 等. 米诺环素相关皮肤色素沉着的研究进展[J]. 药物不良反应杂志, 2021, 23(4): 196-201. [Lu CC, Li WZ, Shen S, et al. Research progress of minocycline-induced skin hyperpigmentation[J]. Adverse Drug Reactions Journal, 2021, 23(4): 196-201.] DOI: 10.3760/cma.j.cn114015-20201119-01153.

13.魏仙妮, 许惠溢, 胡必杰, 等. 米诺环素致光敏反应1例[J].中国药师, 2019, 22(3): 513-514. [Wei XN, Xu HY, Hu BJ, et al. One case of photosensitivity reaction caused by minocycline[J]. China Pharmacist, 2019, 22(3): 513-514.] DOI: 10.3969/j.issn.1008-049X.2019.03.032.

14.Paramo R, Leishangthem L. Optic atrophy secondary to minocycline-induced idiopathic intracranial hypertension[J]. BMJ Case Rep, 2023,16(3): e252731. DOI: 10.1136/bcr-2022-252731.

15.Winn BJ, Liao YJ, Horton JC. Intracranial pressure returns to normal about a monthafter stopping tetracycline antibiotics[J]. Arch Ophthalmol, 2007, 125: 1137-1138. DOI: 10.1001/archopht.125.8.1137.

16.张晓, 田田. 不同性别特发性颅内高压患者的临床特征差异[J]. 河南医学研究, 2022, 31(11): 1946-1950.[Zhang X, Tian T. Differences in clinical characteristics of patients with idiopathic intracranial hypertension of different genders[J]. Henan Medical Research, 2022, 31(11): 1946-1950.] DOI: 10.3969/j.issn.1004-437X.2022.11.007.

17.Shen HX, Liu C, Lin HJ, et al. The efficacy and safety of minocycline as adjuvant therapy in refractory mycoplasma pneumonia in Chinese children: a meta-analysis[J]. Ital J Pediatr, 2022, 48(1):176. DOI: 10.1186/s13052-022-01362-y.

18.曾娜, 王小洁, 孙华君. 米诺环素治疗儿童难治性肺炎支原体肺炎的用药安全性分析[J]. 药学服务与研究, 2020, 20(2): 137-139. [Zeng N, Wang XJ, Sun HJ. Safety analysis of minocycline in the treatment of refractory Mycoplasma pneumoniae pneumonia in children[J]. Pharmaceutical Care and Research, 2020, 20(2): 137-139.] DOI: 10.5428/pcar20200213.

19.Deshayes S, Dolladille C, Dumont A, et al. A worldwide pharmacoepidemiologic update on drug-induced antineutrophil cytoplasmic antibody-associated vasculitis in the era of targeted therapies[J]. Arthritis Rheumatol, 2022, 74(1): 134-139. DOI: 10.1002/art.41902.