Signal Mining and Analysis of Adverse Reactions Induced by Tacrolimus and Voriconazole

doi:10.19803/j.1672-8629.2021.05.17

Abstract

Abstract: Objective To mine and analyze signals of adverse reactions due to the combined use of immunosuppressive agents tacrolimus and voriconazole by using the FDA ( Food and Drug Administration) adverse event reporting system (FAERS) and to provide reference for clinical combined medication. Methods Adverse event reports related to tacrolimus and voriconazole collected in the FAERS database between January 1, 2010 and December 31, 2019 were retrieved using measures of disproportionality. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to compare the suspected adverse reaction signals of tacrolimus and voriconazole used alone or in combination. Adverse reactions that arose from the combination of the two drugs were compared with those specified in the instructions of the two drugs in order to screen out new adverse reactions. Results A total of 52 572 adverse reaction reports of tacrolimus, 8 789 adverse reaction reports of voriconazole, and 1 229 adverse reaction reports of tacrolimus combined with voriconazole were retrieved. When the combined use of the two drugs was compared to tacrolimus used alone, it was found that there were 84 adverse reactions, both ROR and PRR of which were greater than 2, compared with 56 adverse reactions for voriconazole. Compared with the adverse reactions specified in instructions of tacrolimus and voriconazole, there were 6 new adverse reactions involved. Conclusion The combination of tacrolimus and voriconazole may induce far more adverse reactions than single use, which deserves clinical attention.

Key words: tacrolimus, voriconazole, adverse event reporting system, proportional reporting ratio, reporting odds ratio

CLC Number:

R994.11

CAO Xin, SUN Yuquan, HUANG Guimin, RAN Zhongyang, CUI Xiangli. Signal Mining and Analysis of Adverse Reactions Induced by Tacrolimus and Voriconazole[J]. Chinese Journal of Pharmacovigilance, 2021, 18(5): 483-488.

References

[1] Jeong S,Nguyen PD,Desta Z.Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes:major effect on CYPs 2B6,2C9,2C19,and 3A[J].Antimicrobial Agents and Chemotherapy,2009,53(2):541-551.
[2] Voriconazole for injection (Vfend)[EB/OL].(2016-05-11)[2018-10-08].http://www.nbdyf.com/yaopinmulu/3429.html.
[3] Chen K,Zhang XL,Ke XY,et al.Individualized medication of voriconazole:A practice guideline of the division of therapeutic drug monitoring,Chinese pharmacological Society[J].Therapeutic Drug Monitoring,2018,40(6):663-674.
[4] Liu ZY,Chen K,Liu YY,et al.Pharmacokinetic impact of voriconazole on immunosuppressors:A systematic review[J].Clinical Medication Journal(临床药物治疗杂志),2016,14(6):21-26.
[5] Shi BY,Yuan M.Guidelines for immunosuppressive therapy for renal transplant recipients in China(2016)[J].Organ Transplantation(器官移植),2016,7(5):327-331.
[6] Davis S,Gralla J,Klem P,et al.Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation[J].Am J Transplant,2018,18(4) :907-915.
[7] Wei PJ,Shang X,Hu BX.Elevated blood glucose caused by tacrolimus in 1 case[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2014,11(10):636-640.
[8] U.S.Food and drug administration.FDA Adverse event reporting system (FAERS) quarterly data extract files[EB/OL].(2019-08-01)[2020-01-15].https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/33a0f68e-845c-48e2-bc81-8141c6aaf772/state/analysis.
[9] Yoshimura K,Kadoyama K,Sakaeda T,et al.A survey of the FAERS database concerning the adverse event profiles of α1-adrenoreceptor blockers for lower urinary tract symptoms[J].International Journal of Medical Sciences,2013,10(7):864-869.
[10] Bu QY,Xiong NN,Zhou JD,et al.ICH International dictionary of medical terms (MedDRA) :a collection of standard medical terms for pharmaceutical administration[J].Chinese Journal of Clinical Pharma-Cology and Therapeutics(中国临床药理学与治疗学),2007(5):586-590.
[11] Egberts ACG,Meyboom RH,B van puijenbroek EP,et al.Use of measures of dispro-portionality in pharmacovigilance:three dutch examples[J].Drug Safety,2002,25(6):453-458.
[12] Cheng Y,Chen C,Yu CF,et al.Mining and analysis of adverse drug reaction signals caused by tacrolimus based on the U.S.Food and drug administration adverse event reporting system database[J].Evaluation and Analysis of Drug-use in Hospitals of China(中国医院用药评价与分析),2020,20(5):620-624.
[13] Uno T,Wada K,Hosomi K,et al.Drug interactions between tacrolimus and clotrimazole troche:a data mining approach followed by a pharmacokinetic study[J].European Journal of Clinical Pharmacology,2020,76(1):117-125.
[14] Li YY,Zhang Y,Shen AZ.Research progress in adverse drug reaction signal detection methods based on spontaneous reporting system[J].Anhui Medical and Pharmaceutical Journal(安徽医药),2015,19(7):1233-1236.
[15] Harpaz R,Chase HS.Mining multi-item drug adverse effect associations in spontaneous reporting systems[J].BMC Bioin-formatics,2010,11(Suppl 9):S7.
[16] Sakaeda T,Tamon A,Kadoyama K,et al Data mining of the public version of the FDA Adverse event reporting System[J].International Journal of Medical Sciences,2013,10(7):796-803.