(232) Purine Antimetabolites Associated with Pneumocystis Jiroveci Pneumonia: A Disproportionality Analysis in a Spontaneous Reporting Database

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1277

Presenting Author(s)

Lipin Lukose, PharmD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India

Co-Author(s)

Gursimran Kaur, PharmD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India
Beulah E. Thomas
– Hemato-oncology clinical pharmacist and Bone marrow transplant co-ordinator, Sparse Hospital, Bengaluru, Karnataka, Karnataka, India
Subeesh Kulangara Viswam, MPharm
– Assistant Professor, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi, Karnataka, India

Background: Purine antimetabolites are used for various conditions but the incidence of Pneumocystis jiroveci infection associated with its use is not well established.

Objectives: To detect the possible safety signal of purine antimetabolites associated with pneumocystis jiroveci pneumonia through disproportionality analysis in FDA Adverse Event Reporting System (FAERS) Database.

Methods: The case/non-case retrospective disproportionality analysis was performed in a publicly available FAERS database using Open Vigil 2.1(2004Q1-2021Q3). The preferred term used for the study was “pneumocystis jiroveci pneumonia” and the drugs included in the analysis were azathioprine, mercaptopurine, thioguanine, clofarabine, pentostatin, cladribine and fludarabine. Proportional reporting ratio (PRR) and Reporting odds ratio (ROR) was used as the data mining algorithm for the analysis. A value of ROR-1.96SE>1 and PRR>2 with an associated X2 value of 4 or more was considered as the threshold for a signal.

Results: FAERS database had a total of 4330 reports associated with pneumocystis jiroveci pneumonia, out of which 319 reports were associated with purine antimetabolites. Significant signals were obtained for azathioprine[(ROR 15.6(95%CI=13.4-18.1) and PRR 15.5(13.4-17.9)], mercaptopurine[(ROR 11(8-15.2) and PRR 11(8-15.1)], thioguanine [(ROR 31.3(16.7-58.4) and PRR 30.8(16.7-57.1)] and fludarabine [(ROR 14.9 (11.9-18.5) and PRR 14.8 (11.9-18.4)] associated pneumocystis jiroveci infection(PJP). The observed association revealed that females had higher PRR value of 2.86 and 2.18 times for fludarabine and mercaptopurine respectively than males. On stratification of age groups, it was seen that azathioprine was associated with a higher PRR value(18.6) in the 65-100 age group while fludarabine had the highest PRR(13.9) in the 0-17 age group. The majority of deaths due to the adverse reaction were seen with azathioprine and fludarabine(44 and 31 respectively) while most cases who developed life-threatening conditions were seen with azathioprine(15).

Conclusions: Our analyses of spontaneous reporting data identified signals for PJP with azathioprine, mercaptopurine, thioguanine and fludarabine. To validate these findings, more research with a superior epidemiological study design of a defined population is required.