CUPRIOR

What it is

CUPRIOR is a trientine tetrahydrochloride 150 mg film-coated tablet formulation. Trientine is a copper-chelating agent whose principal mechanism of action is to eliminate absorbed copper from the body by forming a stable complex that is then eliminated through urinary excretion. Trientine may also chelate copper in the intestinal tract and so inhibit copper absorption.

Approved indications

— Treatment of Wilson's disease in adults, adolescents and children ≥ 5 years intolerant to D-penicillamine therapy.

Dosing overview

CUPRIOR must be given on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed. The recommended initial dose varies by age group. For children over 5 years, the initial dose is 500 to 750 mg trientine dihydrochloride per day (given in divided doses two or three times daily), which may be increased to a maximum of 1,500 mg per day. For adults, the initial dose is 750 to 1,250 mg trientine dihydrochloride per day (given in divided doses two, three or four times daily), which may be increased to a maximum of 2,000 mg per day. The daily dose should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 microgram/dL (3.1 micromol/L).

Key safety warnings

Patients (especially women) should be closely monitored for evidence of iron deficiency anaemia. Trientine is a chelating agent that has been found to reduce serum iron levels. Iron supplementation may be necessary in some cases and concomitant oral iron should be administered at a different time than trientine. The combination of trientine with zinc is not recommended. Worsening of neurological symptoms may occur at the beginning of chelation therapy due to excess of free serum copper during the initial response to treatment. It is possible that this effect may be more evident in patients with pre-existing neurological symptoms. Trientine dihydrochloride was teratogenic in animals at clinically-relevant doses, possibly due to the induction of copper deficiency or zinc toxicity. Fetal brain abnormalities like haemorrhages and haematomas, delayed ossification in the cranium, exencephaly, microcephaly, and hydrocephaly have been observed in mice and rats treated with trientine.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

CUPRIOR was recommended by PBAC in May 2022 for PBS listing for treatment of patients with Wilson disease intolerant to penicillamine/D-penicillamine.

Regulatory history

CUPRIOR 150 mg film-coated tablets were first listed on the ARTG on 28 September 2021. The TGA approved CUPRIOR on 15 July 2021 for the treatment of Wilson's disease in adults, adolescents and children ≥ 5 years intolerant to D-penicillamine therapy, following a positive risk-benefit assessment across quality, nonclinical, and clinical aspects. PBAC did not recommend the submission in November 2021 and March 2022, but changed its recommendation in May 2022.