TRIENTINE DIHYDROCHLORIDE TILLOMED

Treatment should only be initiated by specialist physicians with experience in the management of Wilson’s disease. 4). 0 grams (4-8 capsules) daily in 2 to 4 divided doses. The recommended doses are expressed as grams or mg of the trientine dihydrochloride salt.

Special populations Elderly No dose adjustment is required in elderly patients. Renal impairment There is limited information in patients with renal impairment. 4). Hepatic impairment There is no data available for the use of trientine in patients with impaired liver function.

4). Paediatric population The starting dose in paediatrics is lower than for adults and depends on age and body weight.

Children≥ 5 years:

The weight-based dose is not established, but the initial dose generally used is 20 mg/kg/day rounded off to the nearest 250 mg capsule of trientine dihydrochloride given in two – three divided doses. The recommended initial dose of trientine dihydrochloride capsule is usually between 500-1250 mg (2-5 capsules).

The maintenance dose is titrated according to clinical response and serum copper level.

Children aged < 5 years:

The safety and efficacy of trientine in children aged < 5 years have not been established. No data are available. Method of administration For oral use. The capsules should be swallowed with water. 5).

Summary of the safety profile Nausea can commonly occur on initial treatment and occasionally skin rash can occur. Duodenitis and severe colitis have been reported. Neurological deterioration can occur at the start of the treatment. Tabulated list of adverse reactions The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).

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). System organ class Adverse reactions Blood and lymphatic system disorders Uncommon: anaemia, aplastic anaemia, sideroblastic anaemia.

Nervous system disorders Uncommon: dystonia, tremor. Not known: dysarthria, muscle rigidity, neurological deterioration. Immune system disorders Not known: lupus-like syndrome, lupus nephritis. Gastrointestinal disorders Common: nausea.

Not known: duodenitis, colitis. Skin and subcutaneous tissue disorder Uncommon: rash. 2). Paediatric population Clinical trials with trientine including a limited number of children in the age range of 5 to 17 years at the start of treatment indicate that frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

When switching a patient from another formulation of trientine, caution is advised because the doses expressed may not be equivalent due to differences in bioavailability. 2). Trientine is a chelating agent which has been found to reduce serum iron levels.

Iron supplements may be necessary in some cases. 5). 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. 5). In patients who were previously treated with D-penicillamine, lupus-like reactions have been reported during subsequent treatment with trientine, however it is not possible to determine if there is a causal relationship with trientine.

Monitoring Patients receiving trientine should remain under regular medical supervision and be monitored using all available clinical data for appropriate control of clinical symptoms and copper levels in order to optimise treatment.

Frequency of monitoring is recommended to be at least twice a year. 2). The aim of maintenance treatment is to maintain free copper levels in plasma (also known as non-ceruloplasmin plasma copper) and the urinary copper excretion within the acceptable limits.

The determination of serum free copper, 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), can be a useful index for monitoring therapy.

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.

The use of appropriate copper parameter target ranges is described in clinical practice guidelines related to Wilson's disease. 6) since copper is required for proper growth and mental development. Therefore, monitoring for manifestations of overtreatment should be undertaken.

Patients with renal and/or hepatic impairment receiving trientine should remain under regular medical supervision for appropriate control of symptoms and copper levels. 2). 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. It is recommended to monitor patients closely for such signs and symptoms and to consider careful titration to reach the recommended therapeutic dose and to reduce dose when necessary.

Dose adjustments in the trientine dose should be considered in case of signs of reduced efficacy such as (persistent) increase in liver enzymes, and worsening of tremor. When trientine doses are adjusted this should be done in small steps.

The trientine dose may also be reduced in case of side effects of trientine, such as gastrointestinal complaints and haematological changes. Trientine doses should be reduced to a more tolerable dose and may be increased again, once side effects have been resolved.

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