Pharmacovigilance-based drug repurposing: searching for putative drugs with hypohidrosis or anhidrosis adverse events for use against hyperhidrosis

Abstract

Background Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing. Objectives We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents. Methods In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined. Results There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation. Conclusions Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.

Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: A safety analysis of the FDA Adverse Event Reporting System

“…The reporting regions of AE reports are mainly North America [19,20]. With regard to SOC level, endocrine disorders, immune system disorders, reproductive system and breast disorders, and surgical and medical procedures were not detected in bosutinib; pregnancy, puerperium and perinatal conditions was not detected in bosutinib and ponatinib; psychiatric disorders was not detected in dasatinib; social circumstances was not detected in dasatinib and bosutinib.…”

“…Atelectasis (13), Bronchial hyperreactivity (5), Dry throat (7), Hypoxia (20), Idiopathic pneumonia syndrome (4), Lung in ltration (8), Nasal oedema (5), Obliterative bronchiolitis (7), Pharyngeal erythema (6), Pleuritic pain (5), Pulmonary granuloma (6), Pulmonary oedema (34), Rales (9), Snoring ( 5…”