Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects

Abstract

From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers’ Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs. However, the pathogenesis of interstitial lung disease (ILD), a serious drug-induced adverse effect, remains unclear. Moreover, there have been no large-scale evaluations of potential complications associated with currently used antiandrogens, which are commonly employed to treat prostate cancer. Hence, ILD, as an adverse event, remains poorly understood. Therefore, we conducted a survey of reports in the Japanese Adverse Drug Event Report (JADER) database to investigate the potential association between the reporting of ILD and antiandrogen drug use in clinical practice. The occurrence of ILD was investigated by evaluating the relationship between antiandrogen drug use and ILD. Adverse event signals were detected with reporting odds ratios (RORs), using data from the JADER and FDA Adverse Event Reporting System (FAERS) databases, for the analysis of post-marketing adverse event reports. The JADER was used to examine the time profile of adverse event occurrence for each drug, whereas the FAERS was used to screen cases of unknown adverse events and analyze their trends of occurrence. The analysis of data from both databases revealed the 95% confidence interval lower limits of ROR for bicalutamide and flutamide to be > 1, and adverse event signals were detected following the use of either drug. While caution should be exercised for drugs that are new to the market, we conclude that drugs with similar therapeutic effects that have been in use for a long period should also be re-examined for potential adverse events.

Interstitial lung disease induced by apalutamide therapy for castration‐resistant prostate cancer: A report of a rare case

“…In general, drug‐induced ILD tends to occur between 2–3 weeks and 2–3 months after drug administration 8 . For apalutamide, drug‐induced ILD was seen within 3 months in this case and in previously published literature 11,12 …”

“…8 For apalutamide, drug-induced ILD was seen within 3 months in this case and in previously published literature. 11,12 When diagnosing suspected cases of drug-induced lung injury, assessing subjective symptoms, along with SpO 2 , the timing of drug initiation or change, drug dosage, and treatment duration is beneficial. If respiratory symptoms and decreased SpO 2 are observed, chest X-ray and CT scans should be performed.…”

Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database

“…Large-scale health information databases are beginning to be used in drug discovery and development. More than 3 million spontaneous reports of adverse events have been registered in FAERS, making it an effective tool for comprehensive risk assessment of adverse drug events and drug repositioning studies [ 26 , 27 , 28 , 29 ]. While this database has the weakness that it does not contain information on all patients who have used a particular drug, but only those who have reported adverse events, it has the strength of being able to analyze a large number of cases in clinical practice.…”

Editorial Comment to Interstitial lung disease induced by apalutamide therapy for castration‐resistant prostate cancer: A report of a rare case

“…The incidence of ILD is higher in Asian patients than in Western patients 4 . When ILD is suspected, any drug that can possibly induce lung injury is usually discontinued promptly, regardless of its severity, and anti‐neoplastic therapy is not resumed until the patient’s lung injury has improved 5 . Additionally, due to the increased risk of perioperative respiratory complications, post‐chemotherapy surgery may be impossible 5 .…”

“…When ILD is suspected, any drug that can possibly induce lung injury is usually discontinued promptly, regardless of its severity, and anti‐neoplastic therapy is not resumed until the patient’s lung injury has improved 5 . Additionally, due to the increased risk of perioperative respiratory complications, post‐chemotherapy surgery may be impossible 5 . Furthermore, due to the COVID‐19 pandemic, all patients who have respiratory distress and/or bilateral ground‐glass opacities on imaging studies need to have COVID‐19 ruled out.…”