Zinc

The absorption of zinc may be reduced by iron and calcium supplements, tetracyclines and phosphorus-containing compounds, while zinc may reduce the absorption of iron, tetracyclines, fluoroquinolones.

Pharmacodynamic studies were conducted in Wilson’s disease patients on the combination of zinc (50 mg three times daily) with ascorbic acid (1 g once daily), penicillamine (250 mg four times daily), and trientine (250 mg four times daily). They showed no significant overall effect on copper balance although mild interaction of zinc with chelators (penicillamine and trientine) could be detected with decreased faecal but increased urinary copper excretion as compared with zinc alone. This is probably due to some extent of complexion of zinc by the chelator, thus reducing the effect of both active substances.

When switching a patient on chelating treatment to zinc for maintenance therapy, the treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for the zinc treatment to induce maximum metallothionein induction and full blockade of copper absorption. The administration of the chelating treatment and zinc should be separated by at least 1 hour.

Data on a limited number of exposed pregnancies in patients with Wilson’s disease give no indication of harmful effects of zinc on embryo/foetus and mother. Five miscarriages and 2 birth defects (microcephaly and correctable heart defect) were reported in 42 pregnancies.

Animal studies conducted with different zinc salts do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

It is extremely important that pregnant Wilson’s disease patients continue their therapy during pregnancy. Which treatment should be used, zinc or chelating agent should be decided by the physician. Dose adjustments to guarantee that the foetus will not become copper deficient must be done and close monitoring of the patient is mandatory.

Zinc is excreted in human breast milk and zinc-induced copper deficiency in the breast-fed baby may occur. Therefore, breast-feeding should be avoided during zinc therapy.

No studies on the effects on the ability to drive and use machines have been performed.

Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Blood and lymphatic system disorders

Uncommon: sideroblastic anaemia, leukopenia

Gastrointestinal disorders

Common: gastric irritation

Investigations

Common: blood amylase, lipase and alkaline phosphatase increased

Anaemia may be micro-, normo- or macrocytic and is often associated with leukopenia. Bone marrow examination usually reveals characteristic “ringed sideroblasts” (i.e. developing red blood cells containing iron-engorged paranuclear mitochondria). They may be early manifestations of copper deficiency and may recover rapidly following reduction of zinc dosage. However, they must be distinguished from haemolytic anaemia which commonly occurs where there is elevated serum free copper in uncontrolled Wilson’s disease.

The most common undesirable effect is gastric irritation. This is usually worst with the first morning dose and disappears after the first days of treatment. Delaying the first dose to mid-morning or taking the dose with a little protein may usually relieve the symptoms.

Elevations of serum alkaline phosphatase, amylase and lipase may occur after a few weeks of treatment, with levels usually returning to high normal within the first one or two years of treatment.