Pharmacokinetics in children

Absorption : in the small intestine, slowed down by numerous food components. Bioavailability = approx. 7%.    Stored primarily in the liver. Elimination: primarily via the faeces and also a small proportion via the urine and by transpiration.  
T½ = approx. 1 hour.

 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects

No information is present at this moment.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

If the child is unable to swallow capsules, they should be opened and the contents dissolved in a little water (sweetened with a little sugar or syrup if needed).

Wilzin must be taken on an empty stomach at least 1 hour before a meal or 2-3 hours after. In cases of gastric intolerance, which often occurs for the early morning dose, that dose can be postponed until mid-morning, halfway between breakfast and lunch. It is also possible to take Wilzin along with a little protein, such as meat.

From the SPC Wilzin 25 mg capsules (Recordati Rare Diseases, EU/1/04/286/001/NO, update date 18.12.2024):

• Zinc acetate dihydrate is not recommended for the initial therapy of symptomatic patients because of its slow onset of action. Symptomatic patients must be initially treated with a chelating agent; once copper levels are below toxic thresholds and patients are clinically stable, maintenance treatment with Wilzin can be considered.
• Nevertheless, while awaiting zinc induced duodenal metallothionein production and consequential effective inhibition of copper absorption, zinc acetate dehydrate could be administered initially in symptomatic patients in combination with a chelating agent.
• Although rare, clinical deterioration may occur at the beginning of the treatment, as has also been reported with chelating agents. Whether this is related to mobilisation of copper stores or to natural history of the disease remains unclear. A change of therapy is recommended in this situation.
• Caution should be exercised when switching patients with portal hypertension from a chelating agent to Wilzin, when such patients are doing well and the treatment is tolerated. Two patients of a series of 16 died from hepatic decompensation and advanced portal hypertension after being changed from penicillamine to zinc therapy.
• Therapeutic monitoring
  • The aim of the treatment is to maintain the plasma free copper (also known as non-ceruloplasmin plasma copper) below 250 microgram/l (normal: 100-150 microgram/l) and the urinary copper excretion below 125 microgram/24 h (normal: < 50 microgram/24 h). The non-ceruloplasmin plasma copper is calculated by subtracting the ceruloplasmin-bound copper from the total plasma copper, given that each milligram of ceruloplasmin contains 3 micrograms of copper.
  • The urinary excretion of copper is an accurate reflection of body loading with excess copper only when patients are not on chelation therapy. Urinary copper levels are usually increased with chelation therapy such as penicillamine or trientine.
  • The level of hepatic copper cannot be used to manage therapy since it does not differentiate between potentially toxic free copper and metallothionein bound copper.
  • In treated patients, assays of urinary and/or plasma zinc may be a useful measure of treatment compliance. Values of urinary zinc above 2 mg/24 h and of plasma zinc above 1250 microgram/l generally indicate adequate compliance.
  • Like with all anti-copper agents overtreatment carries the risk of copper deficiency, which is especially harmful for children and pregnant women since copper is required for proper growth and mental development. In these patient groups, urinary copper levels should be kept a little above the upper limit of normal or in the high normal range (i.e. 40 – 50 microgram/24 h).
  • Laboratory follow-up including haematological surveillance and lipoproteins determination should also be performed in order to detect early manifestations of copper deficiency, such as anaemia and/or leukopenia resulting from bone marrow depression, and decrease in HDL cholesterol and HDL/total cholesterol ratio.
  • As copper deficiency may also cause myeloneuropathy, physicians should be alert to sensory and motor symptoms and signs which may potentially indicate incipient neuropathy or myelopathy in patients treated with Wilzin.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Reference

1. Orphan Europe SARL, SPC Wilzin (EU/1/04/286/002) Rev 11; 14-06-2019, www.ema.europa.eu

Changes