ABSTRACT
Background
D-penicillamine (D-pen) is a copper-chelating drug and has immune-modulatory properties. D-pen is used to treat rheumatoid arthritis, Wilson’s disease, and kidney stones (cystinuria). However, associated adverse events (AEs) of D-pen treatment are frequent and often serious. Therefore, a comprehensive assessment of the safety profile of D-pen is urgently needed.
Research design and methods
We identified and analyzed AEs associated with D-pen between April-1970 to July-2020 from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) databases and calculated the reported odds ratio (ROR) with 95% confidence intervals (CI) using the disproportionality analysis.
Results
A total of 9,150,234 AEs related to drugs were reported in the FAERS database, of which 542 were related to D-Pen. We report that D-pen was associated with dystonia (ROR: 20.52; 95%CI: 12.46–33.80), drug hypersensitivity (ROR: 5.42; 95%CI: 3.72–7.90), pancytopenia (ROR: 10.20; 95%CI: 5.61–18.56), joint swelling (ROR: 9.07; 95%CI: 5.51–14.94), renal-impairment (ROR: 6.68; 95%CI: 3.67–12.15), dysphagia (ROR: 5.05; 95%CI: 2.76–8.89), aggravation of condition (ROR: 4.16; 95%CI: 2.60–6.67), congestive cardiac failure (ROR: 4.04; 95%CI: 2.22–7.35), peripheral edema (ROR: 3.77; 95%CI: 2.17–6.55), tremor (ROR: 3.46; 95%CI: 2.00–6.01), pyrexia (ROR: 3.46; 95%CI: 2.00–6.01), and gait disturbance (ROR: 2.41; 95%CI: 1.29–4.52).
Conclusions
Patients taking D-pen require close monitoring of renal function, blood counts, immunity, liver, cardiac function, and neurological function. D-pen suppresses immune system which maximizes the risk of infection.
Author contributions
Conceptualization, V.K., A.P.S.; Data curation and Formal analysis, V.K., A.P.S; Investigation, A.P.S., and V.K.; Methodology and Writing—Original draft, V.K., and A.P.S.; Writing—Review and editing, V.K., A.P.S., J-J. K., N.W., and C.G.; All authors have read and agreed to the published version of the manuscript.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.