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Adverse Events with d-penicillamine Therapy in Hepatic Wilson’s Disease: A Single-Center Retrospective Audit

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A Correction to this article was published on 23 February 2022

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Abstract

Background and Objective

There are limited data on the adverse events of d-penicillamine in Wilson's disease (WD) that can result in dose modification or treatment discontinuation. The objective of this study was to observe the adverse events related to d-penicillamine in patients with hepatic WD.

Methods

A retrospective audit of prospectively registered hepatic WD patients at a tertiary care center between December 2006 and January 2020 was carried out. Demographic variables, laboratory parameters, and details of treatment were noted. Adverse events (AEs) related to d-penicillamine treatment, the timing and management of these AEs were analysed.

Results

The study included 112 patients with hepatic WD on d-penicillamine. d-penicillamine intolerance was seen in 28/112 (25%) over 179 person-years. Of the 28 AEs, severe AEs leading to permanent d-penicillamine discontinuation occurred in 16 (57%) [never reintroduced 12 (43%), discontinued after intolerant to rechallenge, 4 (14%)], temporary cessation followed by reintroduction to initial dose 13 (46%) and continuation with reduced dose in 3 (11%) patients. Overall, most common AEs were hematological [16, 57% (pancytopenia n = 8, bicytopenia n = 5 and hemolytic anemia n = 3)] while renal adverse events (n = 7, 25%) constituted the most common indication for permanent discontinuation. Cytopenias developed beyond 12 months of d-penicillamine initiation whereas hemolytic anemia developed within first 3 months. Following d-penicillamine discontinuation in 25 patients, it was reintroduced to initial dose in 13/25 (52%), switched to trientine due to neurological worsening in 2/25 (8%) and switched to zinc in 10/25 (40%). In patients with reintroduction, gradual dose escalation was tolerated in 9/13 (69%) with a recurrence of AEs leading to permanent discontinuation in 4/13 (31%).

Conclusion

D-penicillamine treatment is associated with significant AEs mainly related to blood, kidney, and skin. Temporary cessation of drug with reintroduction at a lower dose is an effective and safe option.

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Acknowledgments

The authors convey their greatest gratitude to Dr. Devesh Kumar for performing statistical analysis.

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Authors and Affiliations

  1. Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Gastroenterology office, 9th floor, New Building, Parel, Mumbai, 400012, India

    Sanjay Kumar, Biswa Ranjan Patra, Mohammed Irtaza, Praveen Kumar Rao, Suprabhat Giri, Harish Darak, Amrit Gopan, Aditya Kale & Akash Shukla

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  1. Sanjay Kumar
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  2. Biswa Ranjan Patra
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  3. Mohammed Irtaza
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  4. Praveen Kumar Rao
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Corresponding author

Correspondence to Akash Shukla.

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Funding

No funding was received to conduct this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Institutional Ethics committee, Seth GS Medical college & KEM Hospital (EC/OA 63/2020).

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Informed consent was obtained from all individual participants included in the study.

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Kumar, S., Patra, B.R., Irtaza, M. et al. Adverse Events with d-penicillamine Therapy in Hepatic Wilson’s Disease: A Single-Center Retrospective Audit. Clin Drug Investig 42, 177–184 (2022). https://doi.org/10.1007/s40261-022-01117-x

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  • DOI: https://doi.org/10.1007/s40261-022-01117-x

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