Cuprior · 4.4 Special warnings and precautions for use · 1

HOS-217039 · has-adverse-reaction-information · PDF-Seite 5

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. Tabulated 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). System organ class Adverse reactions Blood and lymphatic system disorders Uncommon: sideroblastic anaemia. 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. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

HOS-217035 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-217034 · has-indication-information · PDF-Seite 2

Cuprior is indicated for the treatment of Wilson’s disease in adults, adolescents and children ≥ 5 years intolerant to D-penicillamine therapy.

HOS-217037 · has-interaction-information · PDF-Seite 4

No interaction studies have been performed. 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. As trientine is poorly absorbed following oral intake and the principal mechanism of action requires its systemic exposure (see section 5.1), it is important that the film-coated tablets are taken on empty stomach at least one hour before meals or 2 hours after meals and at least one hour apart from any other medicinal product, food, or milk (see section 4.2). This maximises the absorption of trientine and reduces the likelihood of the medicinal product binding to metals in the gastrointestinal tract. However, no food interaction studies have been performed and so the extent of the food effect on systemic trientine exposure is unknown. Although there is no evidence that calcium or magnesium antacids alter the efficacy of trientine, it is good practice to separate their administration.

HOS-217038 · has-pregnancy-information · PDF-Seite 4

Pregnancy 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 (see section 5.3). Cuprior 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 (see section 5.3). 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 (see section 4.4). 4 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. Breast-feeding 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 Cuprior therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility It is unknown whether trientine has an effect on human fertility.

HOS-217036 · has-warning-information · PDF-Seite 3

When switching a patient from another formulation trientine, caution is advised because doses expressed in trientine base may not be equivalent (see section 4.2). 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 (see section 4.5). 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. 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 Cuprior should remain under regular medical supervision and be monitored for appropriate control of symptoms and copper levels in order to optimise the dose (see section 4.2). 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. 3 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. Special populations Overtreatment carries the risk of copper deficiency. Monitoring for manifestations of overtreatment should be undertaken, particularly when copper requirements may change, such as in pregnancy (see section 4.6) and in children where appropriate control of copper levels are required to ensure proper growth and mental development. Patients with renal impairment receiving trientine should remain under regular medical supervision for appropriate control of symptoms and copper l

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