Trientine Other names: Triethylenetetramine

Although there is no evidence that calcium or magnesium antacids alter the efficacy of trientine, it is good practice to separate their administration.

Trientine is a chelating agent which has been found to reduce serum iron levels. Iron supplements may be necessary in case of iron deficiency anaemia and should be administered at a different time.

Trientine has been found to reduce serum iron levels, possibly by reducing its absorption, and iron supplements may be required. Since iron and trientine may inhibit absorption of each other, iron supplements should be taken after at least two hours have elapsed from the administration of trientine.

The combination of trientine with zinc is not recommended. There are only limited data on concomitant use available and no specific dose recommendations can be made.

Patients receiving trientine should remain under regular medical supervision and be monitored for appropriate control of symptoms and copper levels in order to optimise the dose.

The aim of maintenance treatment is to maintain free copper levels in the serum within acceptable limits. The most reliable index for monitoring therapy is the determination of serum free copper which is calculated using the difference between the total copper and the ceruloplasmin-bound copper (normal level of free copper in the serum is usually 100 to 150 microgram/L).

The measurement of copper excretion in the urine may be performed during therapy. Since chelation therapy leads to an increase in urinary copper levels, this may/will not give an accurate reflection of the excess copper load in the body but may be a useful measure of treatment compliance.

Worsening of clinical symptoms, including neurological deterioration, may occur at the beginning of chelation therapy due to excess of free serum copper during the initial response to treatment. Close monitoring is required to optimise the dose or to adapt treatment if necessary.

There is a limited amount of data from the use of trientine in pregnant women.

Studies in animals have shown reproductive toxicity, which was probably a result of trientine-induced copper deficiency.

Trientine should only be used in pregnancy after careful consideration of the benefits compared with the risks of treatment in the individual patient. Factors which need to be born in mind include the risks associated with the disease itself, the risk of those alternative treatments which are available and the possible teratogenic effects of trientine.

Since copper is required for proper growth and mental development, dose adjustments may be required to ensure that the foetus will not become copper deficient and close monitoring of the patient is essential.

The pregnancy should be closely monitored in order to detect possible foetal abnormality and to assess maternal serum copper levels throughout the pregnancy. The dose of trientine used should be adjusted in order to maintain serum copper levels within the normal range.

Babies born to mothers being treated with trientine should be monitored for serum copper levels where appropriate.

It is unknown whether trientine is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from trientine therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Trientine has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reaction with trientine is nausea. Serious iron deficiency anaemia and severe colitis may occur during treatment.

List of adverse reactions

The following adverse reactions have been reported with the use of trientine for Wilson’s disease. 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).

Blood and lymphatic system disorders

Not known: iron deficiency anaemia.

Gastrointestinal disorders

Common: nausea.

Not known: duodenitis, colitis (including severe colitis).

Skin and subcutaneous tissue disorder

Uncommon: skin rash, pruritus, erythema.

Not known: urticaria.