Clinical experience on switching trientine tetrahydrochloride to trientine dihydrochloride in Wilson disease patients

Abstract

This study evaluates the effectiveness and safety of trientine dihydrochloride (TETA 2-HCl) in patients with Wilson disease (WD) following a switch from trientine tetrahydrochloride (TETA 4-HCl). A total of 30 WD patients with stable copper metabolism were identified for treatment with TETA 2-HCl (Cufence™) after prior use of TETA 4-HCl (Cuprior™). Biochemical markers including urinary copper, non-ceruloplasmin bound copper (NCC) and liver function were analyzed at baseline and followed up over 12 months. Safety was assessed based on reported adverse events (AEs). Urinary copper levels and NCC remained stable across all follow-ups, indicating adequate copper metabolism control. Reported AEs during TETA 2-HCl treatment were mostly gastrointestinal discomfort (n = 6). In two patients, progressive elevation of transaminases occurred (despite stable copper metabolism). AEs led to discontinuation of treatment in five cases. Median baseline dose per day was 10.2 mg TETA 4-HCl/kg bodyweight, whereas median baseline dose after therapeutic switch to TETA 2-HCl was 12.8 mg/kg bodyweight. Median daily dose at 12 months did not differ significantly from TETA 2-HCl dose at switching timepoint, with stable biochemical markers and markers of copper metabolism in most (25/30) of the patients. Transitioning from TETA 4-HCl to TETA 2-HCl maintained stable copper parameters and liver function in most of analyzed patients. TETA 2-HCl treatment was generally well tolerated, suggesting that switching medications is safe and effective. In our real-life cohort, adjustment factor of ~1.25× for the switch of TETA 4-HCl to TETA 2-HCl resulted in adequate copper metabolism control.