Resident Tufts University Worcester, Massachusetts, United States
Abstract:
Background: Penicillamine is used to treat canine copper-associated hepatopathy (CAH), but studies on efficacy and tolerability are lacking.
Hypothesis/
Objectives: To determine side effects and therapeutic response to penicillamine in CAH.
Animals: Eighty-one client-owned dogs treated with penicillamine.
Methods: Retrospective observational study between 2013 and 2025. Inclusion criteria were a histopathologic CAH diagnosis, hepatic copper quantification >600 ppm or histological copper score ≥3/5, and adequate follow-up. Hepatic biopsies were graded and staged by WSAVA criteria. Dogs that did and did not normalize ALT within one year were compared using Fisher's Exact test (α=0.05). All dogs were on low copper diets.
Results: Forty-eight of 81 dogs (59%) experienced side effects, including anorexia/hyporexia (24/81, 30%), vomiting (12/81, 14.8%), cytopenias (10/81, 12.3%), proteinuria (10/81, 12.3%), cutaneous reactions (6/81, 7.4%), or diarrhea (3/81, 3.7%). Side effects occurred more often in dogs with copper grade 3-5 disease (39/54, 72.2%) than with grade 0-2 disease (9/27, 33.3%). Thirty-one of 81 dogs (38.3%) normalized ALT. Eleven of 48 dogs (22.9%) with side effects normalized ALT compared to 20/33 (60.6%) without side effects (p = 0.001). Dogs with stage 3–4 disease normalized ALT less often (13/47, 27.7%) than those with stage 0–2 disease (17/33, 51.5%, p = 0.037).
Conclusion/Importance: Nearly 60% of dogs, especially those with advanced disease, experienced penicillamine side effects. ALT normalization occurred in about 40% of dogs treated with penicillamine. Advanced disease and side effects were associated with incomplete response. Early diagnosis and maximizing drug tolerance appear to be important in managing CAH with penicillamine.
