---
title: "Paclitaxel formulations and reported risk of macular oedema: real‑world JADER analysis"
id: "plos-one-2-real-world-analysis-of-macular-oedema-associated-with-paclitaxel-formulations"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-2-real-world-analysis-of-macular-oedema-associated-with-paclitaxel-formulations"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959"
published_at: "2026-07-29T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Paclitaxel formulations and reported risk of macular oedema: real‑world JADER analysis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-2-real-world-analysis-of-macular-oedema-associated-with-paclitaxel-formulations
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959)
- **Published At:** 2026-07-29T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This pharmacovigilance study used the Japanese Adverse Drug Event Report (JADER) database (April 2004–June 2025) to investigate associations between **paclitaxel** (PTX) formulations and **macular oedema (ME)**. - After exclusions, 585,738 spontaneous reports were analysed; 123 reports documented ME (preferred terms: macular oedema, cystoid macular oedema). - PTX exposure was present in 16,192 reports (11,563 conventional PTX; 4,629 nanoparticle albumin‑bound PTX [**nab‑PTX**]). - Disproportionality analysis produced a significant reporting signal for overall PTX (adjusted reporting odds ratio [ROR] 19.5; 95% CI 13.5–28.3). - By formulation, significant adjusted RORs were observed for conventional PTX (9.4; 95% CI 5.5–16.1) and **nab‑PTX** (47.0; 95% CI 30.4–72.8). - Multivariable logistic regression included covariates: sex, age ≥70 years, body weight <50 kg, co‑existing diabetes mellitus, and co‑administration of prostaglandin analogue eye drops. - Diabetes mellitus was associated with increased reporting of ME (adjusted ROR 1.8; 95% CI 1.2–2.9). - Co‑administration of prostaglandin analogue eye drops showed a strong association with ME reporting (adjusted ROR 19.9; 95% CI 8.6–45.7). - The authors conclude PTX formulations are linked to an increased reporting signal for ME and suggest closer ophthalmologic monitoring for patients with diabetes or using prostaglandin analogue eye drops during PTX therapy. - The study is hypothesis‑generating and limited by the nature of spontaneous reporting; absolute incidence and causality cannot be determined from JADER alone. Data and code are available via Figshare and the PMDA JADER resource.
## Clinical Analysis & Structured Key Points
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Real‑world analysis of Macular Oedema associated with Paclitaxel Formulations using the Japanese Adverse Drug Event Report database * Koki Takeda , Contributed equally to this work with: Koki Takeda, Toshinori Hirai Roles Conceptualization, Formal analysis, Writing – original draft * E-mail: k-takeda@dwc.doshisha.ac.jp Affiliation Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0004-7712-5714 ](https://orcid.org/0009-0004-7712-5714 "ORCID Registry") ⨯ * Toshinori Hirai , Contributed equally to this work with: Koki Takeda, Toshinori Hirai Roles Conceptualization, Formal analysis, Writing – original draft Affiliation Department of Pharmacy, Institute of Science Tokyo Hospital, Bunkyo-ku, Tokyo, Japan ⨯ * Ayu Sugioka, Roles Data curation Affiliation Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan ⨯ * Rinka Okamura, Roles Data curation Affiliation Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan ⨯ * Asako Nishimura, Roles Data curation Affiliations Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan, Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan ⨯ * Nobuhito Shibata Roles Project administration Affiliation Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-4476-1237 ](https://orcid.org/0000-0002-4476-1237 "ORCID Registry") ⨯ # Real‑world analysis of Macular Oedema associated with Paclitaxel Formulations using the Japanese Adverse Drug Event Report database * Koki Takeda, * Toshinori Hirai, * Ayu Sugioka, * Rinka Okamura, * Asako Nishimura, * Nobuhito Shibata ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: July 29, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0354959) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0354959) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0354959) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0354959) * [Peer Review](https://journals.plos.org/plosone/article/peerReview?id=10.1371/journal.pone.0354959) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#sec005) * [Materials and methods](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#sec006) * [Results](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#sec010) * [Discussion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#sec013) * [Supporting information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#sec014) * [Acknowledgments](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#ack) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0354959) * [Figures](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959) ## Abstract ### Aim This study explored the potential association between paclitaxel (PTX) and macular oedema (ME), a rare adverse event, through pharmacovigilance analysis using a large-scale spontaneous reporting database. ### Methods Disproportionality analysis of ME associated with PTX formulations, including nanoparticle albumin-bound PTX (nab‑PTX) was conducted using the Japanese Adverse Drug Event Report database on data collected during April 2004–June 2025. Multivariable logistic regression analysis was used to estimate adjusted reporting odds ratios (RORs) for ME. A positive signal was defined as a lower 95% confidence interval (CI) for the ROR exceeding 1.0 with at least three ME cases. ### Results Among 585,738 reports, 123 involved ME. A significant signal was observed for overall PTX (adjusted ROR: 19.5; 95% CI: 13.5–28.3). By formulation, significant signals were identified for conventional PTX (adjusted ROR: 9.4; 95% CI: 5.5–16.1) and nab‑PTX (adjusted ROR: 47.0; 95% CI: 30.4–72.8). Multivariable logistic regression indicated significant signals for diabetes mellitus (adjusted ROR: 1.8; 95% CI: 1.2–2.9) and co-administration of prostaglandin analogue eye drops (adjusted ROR: 19.9; 95% CI: 8.6–45.7). ### Conclusion PTX formulations were associated with an increased reporting signal of ME. Notably, patients with diabetes mellitus and those using prostaglandin analogue eye drops may require closer ophthalmologic monitoring during PTX therapy. ## Figures ![Table 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t003) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.g001) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t002) ![Table 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t003) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.g001) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.t002) **Citation:** Takeda K, Hirai T, Sugioka A, Okamura R, Nishimura A, Shibata N (2026) Real‑world analysis of Macular Oedema associated with Paclitaxel Formulations using the Japanese Adverse Drug Event Report database. PLoS One 21(7): e0354959. https://doi.org/10.1371/journal.pone.0354959 **Editor:** Junzheng Yang, Guangdong Nephrotic Drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, CHINA **Received:** April 16, 2026; **Accepted:** July 14, 2026; **Published:** July 29, 2026 **Copyright:** © 2026 Takeda et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** The minimal dataset and accompanying code are available at Figshare via the following DOI: . The original data were obtained from the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency (PMDA).( ) The raw data are publicly available from the PMDA website and are not redistributed here. No, registration or an account is not required to access the JADER database. The data are publicly available and can be freely downloaded from the PMDA website. There are no specific eligibility criteria or access restrictions. The JADER database is openly available to the public. However, users are required to comply with the terms of use specified by the PMDA. Researchers can access the JADER database by visiting the official PMDA website. The dataset can be downloaded from the “Adverse Drug Reaction Report Database” section. The database is provided as downloadable files, which can be obtained directly without any registration. The datasets used in this study were obtained by downloading the relevant files from the PMDA website and processing them for analysis. **Funding:** The author(s) received no specific funding for this work. **Competing interests:** The authors have declared that no competing interests exist. ## Introduction Macular oedema (ME) involves swelling of part of the retina, the light‑sensitive tissue at the back of the eye [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref001)], which can cause visual impairment and markedly reduce quality of life, potentially leading to irreversible blindness in critical cases [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref002)]. The pathophysiology of ME is multi-factorial, involving diabetes mellitus, age‑related macular degeneration, retinitis pigmentosa, uveitis, retinal vein occlusion, ocular surgery and certain medications, including paclitaxel (PTX) [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref003)–[9](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref009)]. Reports of drug‑induced ME are increasing; it can occur unpredictably and is often overlooked in clinical practice [[10](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref010)]. PTX has been reported to induce ME; it binds to tubulin, promoting microtubule polymerisation, which can disrupt retinal pigment epithelial function and cause severe ocular damage [[11](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref011)]. PTX serves as a primary cytotoxic compound integral to established chemotherapy protocols for non-small cell lung cancer (NSCLS) and ovarian cancer [[12](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref012),[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref013)], whereas nanoparticle albumin-bound paclitaxel (nab‑PTX) is used as a core chemotherapy regimen for NSCLS and pancreatic cancer [[12](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref012),[14](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref014)]. However, evidence of PTX‑induced ME from large‑scale analyses remains limited, with only small case reports published [[15](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref015),[16](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref016)]. ME is a rare adverse event, reported in 0.1%–0.4% of cases [[17](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref017)], making evaluation of PTX-associated ME in clinical trials challenging and restricting efforts to prevent ME in clinical practice. The Japanese Adverse Drug Event Report (JADER) database is a spontaneous adverse drug reaction reporting system with extensive and diverse data, allowing hypothesis generation on risk factors for PTX-associated ME. In the present pharmacovigilance study, signal detection analysis of PTX-associated ME was conducted using this database. The analysis aimed to identify potential risk factors and generate hypotheses to guide clinical monitoring and mitigation strategies for ME cases. ## Materials and methods ### Study population and data collection Adverse event (AE) data were obtained from the JADER database on the Pharmaceuticals and Medical Devices Agency (PMDA) website ( ), which is fully anonymised by the PMDA. Individual informed consent was not required as JADER is a publicly accessible database. The JADER database comprised 1,615,041 spontaneous reports integrating demographic information (DEMO), drug administration information, comorbidity information and AE information collected during April 2004–June 2025 ([Fig 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone-0354959-g001)). The analysed dataset was obtained after applying the following exclusion criteria: (1) reports with missing data on sex, age, body weight or reporting year; (2) reports of AEs associated with docetaxel or cabazitaxel; and (3) reports where conventional PTX and nab‑PTX were both registered. Data were pre-screened to remove duplicates and incomplete entries. In the DEMO dataset, age was categorised in 10-year increments, whereas body weight was recorded in 10‑kg intervals. [![thumbnail](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0354959.g001)](https://journals.plos.org/plosone/article/figure/image?size=medium&id=10.1371/journal.pone.0354959.g001 "Click for larger image") Download: * [PNG larger image](https://journals.plos.org/plosone/article/figure/image?download&size=large&id=10.1371/journal.pone.0354959.g001) * [TIFF original image](https://journals.plos.org/plosone/article/figure/image?download&size=original&id=10.1371/journal.pone.0354959.g001) Fig 1. Flowchart of patient selection. Analysed dataset comprised 585,738 reports after excluding (1) records with missing data (n = 1,012,753), (2) reports involving docetaxel or cabazitaxel (n = 16,504) and (3) reports with simultaneous registration of PTX and nab-PTX (n = 46) from the original 1,615,041 reports. In total, 123 cases of ME were identified. [ https://doi.org/10.1371/journal.pone.0354959.g001](https://doi.org/10.1371/journal.pone.0354959.g001) ### AE detection The Japanese version of the Medical Dictionary for Regulatory Activities (MedDRA/J v28.1) was employed as the standardised terminology for coding and analysing AE data. ME events were defined using the preferred term codes for ‘macular oedema’ [10025415] and ‘cystoid macular oedema’ [10058202]. Extracted variables included sex, age, body weight, reporting year, co-existing diabetes mellitus, concomitant prostaglandin analogue eye drop use and ME occurrence. Co-existing diabetes mellitus was specifically defined using preferred terms in the Standardised MedDRA Query for both ‘hyperglycaemia’ and ‘new onset diabetes mellitus’ [20000041]. ### Statistical analysis The signal for ME occurrence was evaluated using disproportionality analysis with a two-by-two contingency table for PTX formulations (conventional PTX and nab-PTX). Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) were calculated according to [equations (1)](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.e001) and [(2)](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.e002): ![](https://journals.plos.org/plosone/article/file?type=thumbnail&id=10.1371/journal.pone.0354959.e001)(1)![](https://journals.plos.org/plosone/article/file?type=thumbnail&id=10.1371/journal.pone.0354959.e002)(2) where _a_ represents patients receiving the target drug with ME, _b_ represents those not receiving the target drug with ME, _c_ represents those receiving the target drug without ME and _d_ represents those not receiving the target drug without ME. A positive signal was defined as a lower 95% CI for the ROR exceeding 1.0 with a minimum of three ME cases [[18](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref018)]. Multivariable logistic regression analysis was performed to calculate adjusted RORs of ME for PTX formulations, incorporating covariates including sex, age (≥70 years), body weight (<50 kg), co-existing diabetes mellitus and co-administration of prostaglandin analogue eye drops. Covariates were selected based on previous studies [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref003),[19](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref019)–[21](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone.0354959.ref021)]. All statistical analyses were performed using R (v4.5.2), with _P_ < 0.05 considered statistically significant. ## Results ### Study population [Fig 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone-0354959-g001) presents a flowchart summarising the selection of the study population. The JADER dataset initially comprised 1,615,041 reports. After applying the following exclusion criteria, 585,738 reports were retained: (1) missing data on sex, age, body weight and reporting year (n = 1,012,753); (2) use of docetaxel or cabazitaxel (n = 16,504); and (3) simultaneous registration of conventional PTX and nab-PTX (n = 46). In the final dataset, 123 reports of ME were identified. [Table 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354959#pone-0354959-t001) summarises the clinical characteristics of the study population. Among the reports, 308,573 (52.68%) were for male patients, 246,824 (42.14%) involved patients aged ≥70 years and 203,737 (34.78%) involved patients weighing <50 kg. Reports for patients receiving the study drugs totalled 16,192 (2.76%), including 11,563 (1.97%) with conventional PTX and 4,629 (0.79%) with nab‑PTX. Co-existing diabetes mellitus was reported in 79,493 cases (13.57%) and 1,770 reports (0.30%) involved co-administered prostaglandin analogue eye drops. [![thumbnail](https://journals.plos.org/plosone/article/figure
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