Introduction
Copper is a tiny but essential mineral that our body needs to work properly. However, too much or too little copper can cause serious health problems. Some genetic disorders disrupt normal copper levels. For example, Menkes disease, caused by mutations in the ATP7A gene, and occipital horn syndrome, also linked to ATP7A mutations, happen when the body doesn’t have enough copper.
In Menkes disease, low copper affects important enzymes, which can harm brain development if not treated early. Doctors treat it with copper-histidine injections, but these only work if started before 2 months of age. Occipital horn syndrome is a milder form and mainly affects connective tissues, but there isn’t a standard treatment for it yet.1
On the other hand, Wilson’s disease, caused by mutations in the ATP7B gene, happens when copper builds up too much in the body, mainly affecting the liver and nervous system. Early detection is tricky, but treatments like chelating agents and zinc can help remove extra copper.
Unfortunately, these treatments may not work well in severe liver problems or some neurological cases. Because early treatment is so important, experts suggest screening infants for Wilson’s disease. Patients with this condition may also have a higher risk of developing liver cancer, making awareness and monitoring essential for prevention and care. 1
What is Syprine (Trientine)?
Syprine (Trientine) is a type of chelation therapy used to treat Wilson disease, a copper-related genetic disorder. Chelation therapy and zinc salts have been used for over 60 years to help the body get rid of excess copper and keep copper levels under control. For Wilson disease, treatment is lifelong. While a liver transplant can fix the liver problem and is usually curative, it’s reserved only for very serious cases like acute liver failure or advanced liver cirrhosis.2
The first oral chelator for Wilson disease was DPA (D-penicillamine), introduced in 1956, which works by binding copper so it can be passed out in urine. Because DPA can interfere with vitamin B6 (pyridoxine), patients also need a small daily B6 supplement. Trientine, introduced in 1969, is chemically different from DPA but works in a similar way, helping the kidneys flush out the copper. Together with dietary copper restriction and zinc salts, these treatments are the main options doctors use to manage Wilson disease. 2
Indications
Trientine is an oral medicine used to treat Wilson disease, a genetic problem where the body can’t properly get rid of extra copper. In Wilson disease, a defect in a liver enzyme called ATPase7B stops copper from being transported and excreted into bile. Because of this, free copper builds up first in the liver and blood, and then in other organs like the brain and kidneys.
This buildup can damage the liver and nervous system and may show up in childhood or the teen years as liver problems, neurological symptoms, or even anemia. Trientine works as a copper chelating agent, which means it binds to the extra copper so the body can safely remove it, helping prevent further copper damage when taken regularly.3
Mechanism of Action
Trientine works by grabbing onto copper in the body and forming a strong, stable bond. Its special polyamine-like structure uses four nitrogen atoms to create a ring that tightly holds the copper. Once bound, this copper-Trientine complex is safely removed from the body through urine.
It was approved in the United States in 1969 and is used for Wilson disease patients who cannot tolerate penicillamine. It comes as 250 mg capsules, with typical doses ranging from 750–1250 mg a day for adults and 500–750 mg for children, split into 2–4 smaller doses. In some cases, the dose can go up to 2000 mg for adults or 1500 mg for children if needed.3
Syprine vs. Penicillamine
Doctors who treat Wilson disease say that not everyone can handle or respond well to penicillamine (DPA) or zinc. About 20%–40% of patients can’t take DPA because of side effects or toxicity, and zinc doesn’t work well or is poorly tolerated in about 30% of patients. These limits leave some people without good treatment choices.
Trientine (Syprine) is often used only after DPA fails, but many experts believe it should be available as a first option. They point out that trientine is easier to take (just twice a day), has fewer side effects, works well, and is usually well tolerated.2
The specialists warn that delaying proper treatment or forcing patients to retry DPA or zinc can cause irreversible harm, especially for people whose disease is already progressing. Trientine can reduce copper levels in most patients, but like all chelators, it can sometimes make neurological symptoms worse at first. This effect seems to happen more often with DPA than trientine, though evidence is limited.2
Role in Long-Term Management
Trientine is used for the long-term management of Wilson disease, and regular monitoring is key to keeping treatment on track. Doctors check how well it’s working using tests like ceruloplasmin-bound copper, 24-hour urine copper levels, and liver function tests. They also look for improvements in liver health and nerve-related symptoms.
In the beginning, patients share how they’re feeling every month, but once things are stable, these check-ins usually happen every 6 to 12 months. Objective tests like brain scans or lab work are done at least once a year, but sometimes more often when treatment is first started.2
For children, these checks are even more frequent (every 3 to 6 months) because their doses are based on weight and may need adjusting. Since treatment for Wilson disease is lifelong, stopping trientine without switching to another therapy can be dangerous. If trientine isn’t working well or causes side effects, another chelator must be started right away. 2
Adverse Effects
Trientine is usually well tolerated, and most side effects are mild. These can include things like headaches, joint or muscle pain, nausea, loss of appetite, diarrhea, skin rash, or some kidney problems.
In rare cases, trientine can cause more serious reactions. These uncommon but potentially severe effects include allergic (hypersensitivity) reactions, lupus-like syndromes, or pancytopenia (a drop in blood cell counts).3
Clinical Evidence
Trientine has been studied as a treatment for Wilson’s disease and shows promising results. In a large study of 405 patients, it worked about as well as penicillamine in improving liver and neurological symptoms. Around 90% of patients on first-line therapy saw their liver problems improve, while about 66% saw neurological improvements. Trientine was generally easier to tolerate than penicillamine, with fewer people stopping treatment due to side effects. Smaller studies with 5–23 patients also support its use, though more research is needed to fully understand how it compares with other treatments like penicillamine and zinc.4
Conclusion
Trientine (Syprine) is an effective and generally well-tolerated option for managing Wilson disease, especially for patients who cannot take penicillamine or need a safer long-term treatment. Regular monitoring and adherence to therapy are essential to keep copper levels under control and prevent complications.
Note:
This content is for informational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare provider regarding diagnosis, treatment, or any questions about a medical condition.
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References:
- Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr Drug Metab. 2012;13(3):237-250. doi:10.2174/138920012799320455
- Trientine Hydrochloride (MAR-Trientine): CADTH Reimbursement Review: Therapeutic area: Wilson disease [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2022 Feb. Clinical Review. Available from: https://www.ncbi.nlm.nih.gov/books/NBK595409/
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Trientine. [Updated 2020 Jul 25]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548119/
- National Institute for Health and Care Excellence. (2016, September). Wilson’s disease: Trientine dihydrochloride – Evidence review. NICE Medicines and Technologies Programme on behalf of NHS England Specialised Commissioning. https://www.nice.org.uk
