Table 1.

Transitioning Between Therapeutic Agents in Wilson Disease^a.

	When to Transition	How to Transition	Monitoring
PCA to trientine	● Patient unable to tolerate PCA ● Development of nephrotic syndrome, severe thrombocytopenia, or aplastic anemia	No taper or overlap indicated	Baseline CBC, CMP, and 24-hour urinary copper prior to switch Repeat above laboratory tests monthly for 3 to 4 months Goal: Maintain 24-hour urinary copper 200 to 500 µg, stable ALT Long-term: Repeat blood tests, including CBC and CMP, and 24-hour urinary copper at least every 6 months; 24-hour urinary copper should be in the 200 to 500 µg/day range
PCA to zinc salts	● Patient unable to tolerate PCA ● Development of renal failure, severe thrombocytopenia/aplastic anemia ● Worsening neurologic symptoms ● Pregnancy	Start zinc at 50 mg TID, uptitrate by 50 mg increments as necessary Continue PCA for at least 3 months after initiating zinc therapy PCA and zinc dosing must be spread out so that they are not taken at the same time; PCA cannot be given at meal times	CMP, 24-hour urinary copper prior to switch and every 3 months until urinary copper at goal/stabilizes Goal: Maintain urinary copper <75 µg, stable liver enzymes Long-term: Repeat blood tests, including CBC and CMP, and 24-hour urinary copper at least every 6 months; 24-hour urinary copper should be <75 µg/day
Trientine to zinc salts	● Financial limitations ● Limited drug availability ● Development of pancolitis ● Pregnancy	Start zinc at 50 mg TID, titrate by 50 mg increments as necessary; when starting zinc, reduce trientine dose by 250 mg and reduce by 250 mg every month until termination of trientine Continue trientine for at least 3 months after initiating zinc therapy Trientine and zinc dosing must be spread out so that they are not taken at the same time; PCA cannot be given at meal times	CMP, 24-hour urinary copper prior to switch and every 3 months until urinary copper at goal/stabilizes Goal: Maintain urinary copper <75 µg, stable liver enzymes Long-term: repeat blood tests, including CBC and CMP, and 24-hour urinary copper at least every 6 months; 24-hour urinary copper should be <75 µg/day
Zinc salts to trientine	● Ineffective therapy demonstrated by uptrending liver enzymes, development of liver synthetic dysfunction	No taper or overlap indicated	Baseline CBC, CMP, and 24-hour urinary copper prior to switch Repeat above laboratory tests monthly for 3 to 4 months Goal: Maintain urinary copper 200 to 500 µg, stable liver enzymes
Trientine or zinc salts to PCA	● Financial limitations ● Patient’s preference	No taper or overlap indicated	Baseline CBC, CMP, and 24-hour urinary copper prior to switch Repeat above laboratory tests monthly for 1 to 2 months Goal: Maintain urinary copper 200 to 500 µg, stable liver enzymes Long-term: Repeat blood tests, including CBC and CMP, and 24-hour urinary copper at least every 6 months; 24-hour urinary copper should be in the 200 to 500 µg/day range Repeat UA every 6 months to check on proteinuria

Abbreviations: PCA, penicillamine; CBC, complete blood count; CMP, complete metabolic panel (including liver enzymes); ALT, alanine transaminase; TID, 3 times a day; UA, urinalysis.

^aDose of zinc refers to elemental zinc.