Trientine
Regulatory sources consulted
Approved indications
- Treatment of Wilson disease in adults, adolescents and children aged 5 years or older who are intolerant of D-penicillamine.
Contraindications
Absolute
- Hypersensitivity to trientine or any excipient.
Clinical warnings
- Major warning · Different trientine salts and formulations may differ in trientine-base content and bioavailability and are therefore not interchangeable. A dose adjustment may be needed when switching formulations. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
- Major warning · Regularly monitor clinical symptoms, plasma free copper and urinary copper excretion. Monitor for overtreatment and copper deficiency, particularly in children and during pregnancy. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
- Major warning · In renal or hepatic impairment, maintain regular medical supervision of symptoms and copper levels, with close monitoring of renal or hepatic function. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
- Major warning · Neurological deterioration may occur when chelation is started because of a transient excess of free copper. Monitor closely and adjust the dose gradually according to clinical response. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
- Trientine reduces serum iron levels; iron supplementation may be needed in some cases and should be administered separately from trientine. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
- Pseudolupus reactions have been reported during trientine treatment in patients previously treated with D-penicillamine, although a causal relationship has not been established. Maintain clinical monitoring. — AEMPS CIMA, Cufence, ficha técnica 1191365001, sección 4.4
Drug interactions
- ModerateZinc
Mechanism: Concomitant administration can reduce the therapeutic effect of both zinc and trientine.
Recommendation: Do not administer concomitantly.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
- ModerateIron supplements
Mechanism: Iron and trientine can each inhibit the other’s absorption.
Recommendation: Separate administration by at least one hour.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
- ModerateFood and milk
Mechanism: Food can reduce trientine absorption by up to 45%.
Recommendation: Take fasting, one hour before or two hours after food; separate from milk and other oral medicines by one hour.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
- ModerateOther heavy metals
Mechanism: Simultaneous administration may form complexes with trientine in the gastrointestinal tract and reduce its absorption.
Recommendation: Administer at least one hour apart from trientine.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
- ModerateCalcium- or magnesium-containing antacids
Mechanism: Although there is no evidence that they alter trientine efficacy, the product information recommends avoiding simultaneous administration.
Recommendation: Separate administration of the antacid and trientine; the product information does not specify an exact interval.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
- ModerateOther anti-copper medicines
Mechanism: Clinical data on concomitant use with other anti-copper medicines are limited.
Recommendation: Manage changes in anti-copper therapy under specialist supervision.
https://cima.aemps.es/cima/dochtml/ft/1191365001/FT_1191365001.html
Adverse events
Common (≥1%)
Nausea
Rare but serious
Aplastic anaemia · Sideroblastic anaemia · Lupus nephritis · Severe colitis · Neurological deterioration
Pregnancy and lactation
Use during pregnancy only after careful benefit-risk assessment. Limited clinical data suggest that trientine is not excreted in human milk, but a risk to the breastfed infant cannot be excluded; decide whether to discontinue breastfeeding or treatment, considering the benefit of breastfeeding for the child and the benefit of treatment for the mother.
Recent literature (PubMed)
Wilson's disease (WD) is an uncommon hereditary disorder caused by a deficiency in the ATP7B transporter. The protein codified by this gene facilitates the incorporation of the copper into ceruloplasmin. Therefore, WD accumulates copper primary in the liver and secondary in other organs, such as the central nervous system. It represents a wide spectrum of disease, ranging from being asymptomatic in some patients to promote an acute liver failure in others. The diagnosis requires a combination of clinical signs and symptoms, as well as some diagnostic tests such as the measurement of serum ceruloplasmin, the urinary excretion of copper, the liver biopsy or the genetic testing. The treatment must be maintained lifelong and includes some drugs such as chelating agents (penicillamine and trientine) and inhibitors of the copper absorption (zinc salts). Lastly, the liver transplant should be an option for patients with end-stage liver disease.
Wilson's disease is an autosomal recessive disorder of copper metabolism which affects the liver, brain and other organs. Diagnosis is based on: clinical features; biochemical tests, including plasma ceruloplasmin concentration, 24-h urinary copper excretion, copper content in the liver; and molecular analysis. Leipzig score and additionally relative exchangeable copper determination are recommended for diagnosis. Pharmacological therapy comprises chelating agents (penicillamine, trientine) and zinc salts, while only chelators are recommended for significant liver disease. Monitoring is based on clinical symptoms, liver tests and copper metabolism (urinary copper excretion, exchangeable copper) to detect poor compliance and over/under-treatment. Acute liver failure is challenging as making a diagnosis is difficult and pharmacological therapy may not be sufficient to save life. Liver transplantation has a well-defined role in Wilsonian acute hepatic failure but may also be considered in neurological disease. Limited information indicates that trientine is not detectable in breastmilk, and no adverse effects have been reported among breastfed infants whose mothers were taking the drug. The effect of trientine on breastmilk copper and zinc concentrations in milk is somewhat conflicting,[1-4]but breastfed infants appear to have normal serum copper and zinc plasma levels. Based on available data, it appears that trientine is acceptable to use during breastfeeding. Wilson disease is a disorder of copper metabolism that, when untreated, can present with hepatic, neurologic, or psychiatric disturbances – or a combination of these – in individuals ages three years to older than 70 years. Manifestations in untreated individuals vary among and within families. Liver disease can include recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations can include dysarth