From the Guidelines
High copper levels are typically treated with chelation therapy using medications like penicillamine, trientine, or zinc acetate, with the most recent and highest quality study 1 recommending zinc therapy (150 mg elemental zinc/day) as a first-line treatment for neurological patients and maintenance therapy.
Treatment Options
- Penicillamine: 250-500mg four times daily, with a high risk of side effects, including worsening of neurologic symptoms in 10-50% of patients 1
- Trientine: 750-1500mg daily in divided doses, with fewer side effects than penicillamine, but still a risk of neurological worsening 1
- Zinc therapy: 150 mg elemental zinc/day, administered in three divided doses, 30 min before meals, with few side effects, including gastric irritation 1
Monitoring and Dietary Modifications
- Regular blood tests to check copper levels, liver function, and complete blood counts
- Dietary modifications, including avoiding copper-rich foods like liver, shellfish, chocolate, nuts, and mushrooms
- Patients should use distilled water if their tap water contains high copper levels
Side Effects and Contraindications
- Penicillamine: severe side effects, including nephrotoxicity, lupus-like syndrome, and bone marrow suppression 1
- Trientine: few side effects, including pancytopenia and lupus-like reactions 1
- Zinc therapy: few side effects, including gastric irritation and immunosuppressant effects 1
From the FDA Drug Label
Treatment has two objectives: (1) to minimize dietary intake of copper; (2) to promote excretion and complex formation (i.e., detoxification) of excess tissue copper. The first objective is attained by a daily diet that contains no more than 1 or 2 mg of copper. For the second objective, a copper chelating agent is used. The active moiety in zinc acetate is zinc cation Regardless of the ligand, zinc blocks the intestinal absorption of copper from the diet and the reabsorption of endogenously secreted copper such as that from the saliva, gastric juice and bile.
Treating high copper levels can be achieved through two main objectives:
- Minimizing dietary intake of copper
- Promoting excretion and complex formation of excess tissue copper using a copper chelating agent, such as penicillamine or zinc acetate. Zinc acetate works by blocking the intestinal absorption of copper and inducing the production of metallothionein, which binds copper and prevents its transfer into the blood. Penicillamine is used to promote excretion and complex formation of excess tissue copper. It is essential to note that zinc acetate is not recommended for initial therapy in symptomatic patients due to the delay in its effects, and penicillamine or other chelating agents should be used initially. Maintenance treatment with zinc acetate can be considered once the patient is clinically stable 2, 3, 3.
From the Research
Treatment Options for High Copper Levels
- The primary treatment options for high copper levels, particularly in the context of Wilson's disease, include zinc, penicillamine, trientine, and tetrathiomolybdate 4, 5, 6.
- Zinc is considered the treatment of choice for maintenance therapy, as well as for presymptomatic and pregnant patients, due to its efficacy and lack of toxicity 4.
- Trientine and zinc may be used in combination for initial treatment of patients with mild liver failure, as trientine provides a strong, fast, negative copper balance, and zinc induces hepatic metallothionein, which sequesters hepatic copper 4.
- Tetrathiomolybdate may be used for initial treatment of patients presenting with neurological disease, as it provides rapid, safe control of copper 4.
Reducing Liver Copper Concentration
- Treatment with 'anti-copper' agents, including penicillamine, trientine, and tetrathiomolybdate, can reduce liver copper levels in patients with Wilson's disease 6.
- The copper concentration in the liver falls rapidly in the first year of treatment, and poor compliers have a higher liver copper concentration than good compliers 6.
Crisis Management in ICU
- In cases of Wilson's disease crisis, therapeutic plasma exchange and albumin dialysis may be used to rapidly reduce serum copper levels, potentially delaying or preventing the need for liver transplantation 7.
Antiangiogenic Anticancer Therapy
- Copper control may have applications in antiangiogenic anticancer therapy, with tetrathiomolybdate showing promise in reducing tumor growth in animal models and human patients 8.