Cufence: Uses, Dosage & Side Effects
A copper chelating agent used to treat Wilson's disease by removing excess copper from the body, for patients who cannot tolerate D-penicillamine
Cufence (trientine dihydrochloride) is an oral copper chelating agent used to treat Wilson's disease in adults, adolescents, and children aged 5 years and older. Wilson's disease is a rare inherited disorder in which the body is unable to properly excrete copper, leading to dangerous accumulation in the liver, brain, cornea, and other organs. Cufence works by binding to excess copper and facilitating its removal through the kidneys. It is specifically intended for patients who cannot tolerate D-penicillamine, the traditional first-line chelation therapy. Cufence is a prescription-only medication that requires lifelong use and regular monitoring of copper levels by a specialist physician.
Quick Facts: Cufence
Key Takeaways
- Cufence (trientine) is a copper chelating agent that removes excess copper from the body by binding to copper ions and promoting their excretion through the kidneys, used specifically for treating Wilson's disease.
- It is indicated for adults, adolescents, and children aged 5 years and older who cannot tolerate D-penicillamine, the traditional first-line therapy for Wilson's disease, due to adverse effects.
- Cufence must be taken on an empty stomach (at least 1 hour before or 2 hours after meals) with water only, as food, milk, and other beverages significantly reduce its absorption and effectiveness.
- Treatment with Cufence is lifelong because Wilson's disease is a chronic genetic condition; stopping therapy can lead to rapid, potentially life-threatening copper re-accumulation.
- Regular monitoring of copper levels in blood and urine is essential, especially at the start of treatment, during dose changes, in growing children, and during pregnancy to ensure optimal copper control.
What Is Cufence and What Is It Used For?
Cufence contains the active substance trientine (also known as triethylenetetramine), which belongs to a class of medications called copper chelating agents. Chelation therapy is a cornerstone of managing Wilson's disease, a rare autosomal recessive genetic disorder caused by mutations in the ATP7B gene. This gene encodes a copper-transporting ATPase protein that is essential for the normal excretion of copper through bile. When this protein is defective, copper cannot be adequately eliminated from the body, leading to progressive accumulation in multiple organs, particularly the liver, brain, cornea, and kidneys.
Wilson's disease (also known as hepatolenticular degeneration) affects approximately 1 in 30,000 people worldwide, though prevalence varies among populations. Without treatment, the disease is invariably fatal. The condition typically presents between the ages of 5 and 35 years, though it can manifest at any age. Liver disease is the most common initial presentation in children and adolescents, while neurological and psychiatric symptoms are more common in adults. The characteristic Kayser-Fleischer rings (golden-brown deposits of copper in the cornea visible on slit-lamp examination) are present in most patients with neurological disease.
Trientine works through a straightforward but highly effective mechanism. The molecule contains four nitrogen atoms arranged in a polyamine chain, each of which can donate electron pairs to form coordinate bonds with copper ions. When trientine encounters free or loosely bound copper in the gastrointestinal tract and bloodstream, it forms a stable, water-soluble chelate complex. This trientine-copper complex is then efficiently excreted through the kidneys in the urine. Additionally, trientine reduces the intestinal absorption of dietary copper by chelating copper within the gastrointestinal lumen before it can be absorbed.
Cufence is specifically indicated for the treatment of Wilson's disease in adults, adolescents, and children aged 5 years and older who cannot take D-penicillamine, the historically first-line copper chelating agent, due to intolerance or adverse effects. D-penicillamine, while effective, causes significant side effects in a substantial proportion of patients, including nephrotoxicity (proteinuria and nephrotic syndrome), bone marrow suppression, lupus-like autoimmune reactions, and skin toxicity. For these patients, trientine provides an effective alternative with a generally more favorable side effect profile.
The goals of copper chelation therapy in Wilson's disease are twofold. During the initial de-coppering phase, treatment aims to mobilize and remove the excess copper that has accumulated in tissues over years. This phase typically lasts several months to years and requires higher doses. Once copper stores have been reduced to safe levels, treatment transitions to a maintenance phase in which lower doses are used to prevent re-accumulation. Throughout both phases, careful monitoring of copper levels in blood (serum free copper or non-ceruloplasmin-bound copper) and 24-hour urinary copper excretion is essential to guide dose adjustments and ensure adequate but not excessive copper removal.
While Wilson's disease is a lifelong genetic condition, it is one of the few genetic metabolic disorders that is entirely treatable. With appropriate copper chelation therapy and/or zinc supplementation, patients can lead normal, healthy lives. Early diagnosis and consistent treatment are critical, as untreated disease leads to progressive liver failure, irreversible neurological damage, or both. Even patients who present with advanced disease can experience significant improvement with proper therapy.
What Should You Know Before Taking Cufence?
Contraindications
There are specific situations in which Cufence must not be used. Understanding these absolute contraindications is essential before starting treatment.
- Hypersensitivity: Do not take Cufence if you are allergic to trientine (triethylenetetramine) or any of the other ingredients in the product. Signs of an allergic reaction include skin rash, itching, facial swelling, dizziness, and difficulty breathing. If you experience any of these symptoms, seek medical attention immediately.
Warnings and Precautions
Problems with the nervous system (such as tremors, loss of coordination, slurred speech, muscle stiffness, and worsening muscle spasms) may occur, particularly in patients who are just starting treatment with Cufence. This paradoxical neurological deterioration is thought to result from the initial mobilization of copper from tissue stores, temporarily increasing free copper levels in the brain. If you experience any of these symptoms while taking Cufence, contact your doctor immediately. In most cases, these symptoms improve with continued treatment, but dose adjustment may be necessary.
Before and during treatment with Cufence, your doctor will carefully monitor your condition. The following points are important to be aware of:
- Regular monitoring: Your doctor must regularly check for symptoms of Wilson's disease and measure copper levels in your blood and urine. Regular monitoring is particularly important at the start of treatment, when doses are being adjusted, in children who are still growing, and in pregnant women. This ensures that copper levels are maintained at an appropriate level – low enough to prevent organ damage but not so low as to cause copper deficiency.
- Dose adjustments: Based on monitoring results, your doctor may need to increase or decrease your dose of Cufence. Inadequate dosing allows copper to continue accumulating, while excessive dosing can cause copper deficiency, which has its own set of complications including anemia and bone marrow suppression.
- Lupus-like reactions: Symptoms resembling systemic lupus erythematosus (including persistent skin rash, joint pain, and fatigue) have been reported in some patients who switched from D-penicillamine to trientine-containing medications. However, it has not been possible to determine whether these reactions were caused by trientine itself or were a delayed consequence of the previous penicillamine therapy. Report any such symptoms to your doctor.
- Gastrointestinal inflammation: In rare cases, trientine may cause inflammation of the small intestine (duodenitis) or large intestine (colitis). If you experience severe abdominal pain or persistent diarrhea, contact your doctor immediately.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine. Managing Wilson's disease during pregnancy requires careful balance. It is critically important to continue copper chelation therapy during pregnancy to maintain normal copper levels and prevent disease flare-ups, which could be life-threatening for both mother and baby. However, the potential risks of the medication to the developing fetus must also be considered.
If you become pregnant while taking Cufence, your doctor will monitor you closely throughout the pregnancy for signs of effects on the baby and for changes in your copper levels. Your doctor will recommend the treatment and dose that is most appropriate for your specific situation. Some specialists may adjust the dose during pregnancy, particularly in the third trimester, to balance adequate copper control with fetal safety.
The limited available information suggests that trientine does not pass into breast milk in significant amounts, but a risk to the nursing infant cannot be entirely excluded. Your doctor will help you decide whether to continue breastfeeding or to discontinue Cufence, taking into account the benefit of breastfeeding for the child and the benefit of treatment for you. All decisions regarding medication use during pregnancy and breastfeeding should be made in close consultation with your hepatologist or specialist physician.
Abruptly stopping copper chelation therapy during pregnancy is extremely dangerous and can lead to acute liver failure due to rapid copper re-accumulation. Always consult your doctor before making any changes to your treatment, even if you discover you are pregnant.
How Does Cufence Interact with Other Drugs?
Drug interactions are an important consideration for patients taking Cufence. Tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or might take, including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. Because trientine is a chelating agent, it has the potential to bind to various metal ions and interfere with the absorption of other medications.
The most clinically significant interactions involve substances that contain metal ions or that alter the pH of the gastrointestinal environment. These interactions can significantly reduce the bioavailability of trientine, rendering it less effective at removing copper from the body. Conversely, trientine can also reduce the absorption of certain other medications by binding to them in the gut.
Major Interactions
| Interacting Substance | Effect | Recommendation |
|---|---|---|
| Iron supplements | Iron can bind to trientine in the gut, reducing absorption of both the iron and trientine | Separate by at least 2 hours before or after Cufence |
| Antacids (e.g., aluminum/magnesium hydroxide, calcium carbonate) | Metal ions in antacids can chelate with trientine; altered gastric pH may reduce absorption | Separate by at least 2 hours before or after Cufence |
| Zinc supplements | Trientine may chelate zinc; zinc and trientine may interfere with each other's mechanisms | If used together for Wilson's disease, separate doses by at least 1 hour; discuss with specialist |
Minor Interactions and General Precautions
| Interacting Substance | Effect | Recommendation |
|---|---|---|
| Other oral medications | Trientine may bind to other drugs in the gastrointestinal tract, potentially reducing their absorption | Take all other medications at least 1 hour apart from Cufence |
| Mineral supplements (calcium, magnesium, multivitamins with minerals) | Divalent and trivalent metal ions may compete with copper for binding to trientine | Separate by at least 2 hours; discuss with your doctor |
| Copper-rich foods | High dietary copper intake can counteract the effects of chelation therapy | Avoid high-copper foods: liver, shellfish, nuts, chocolate, mushrooms, and organ meats |
It is important to note that food and beverages other than water can significantly reduce the absorption of Cufence. For this reason, the medication must be taken with water only, on an empty stomach. Avoid eating or drinking anything (except water) for at least 2 hours before and 1 hour after taking Cufence. Milk is particularly problematic as it contains calcium and other minerals that can bind to trientine and reduce its effectiveness.
Many patients with Wilson's disease take multiple medications throughout the day. A useful strategy is to plan a medication schedule with your pharmacist or doctor. For example, you might take Cufence first thing in the morning on an empty stomach, wait at least 1 hour before eating breakfast or taking other medications, and then take your second dose of Cufence at least 2 hours after lunch. Keeping a written schedule can help ensure proper timing and maximize the effectiveness of all your medications.
What Is the Correct Dosage of Cufence?
Always take this medicine exactly as your doctor or pharmacist has told you. Your doctor will determine the most appropriate dose for you based on your copper levels, clinical response, body weight, and other individual factors. Do not change your dose without consulting your doctor, even if you feel well.
Adults (Including Elderly)
Adult Dosing
The usual dose for adults ranges from 800 to 1,600 mg daily, taken orally. The total daily dose is typically divided into 2 to 4 smaller doses as directed by your doctor. During the initial de-coppering phase, higher doses within this range may be necessary to mobilize accumulated copper stores. Once copper levels are adequately controlled (maintenance phase), your doctor may reduce the dose to the lower end of the range.
Children and Adolescents (5 to 17 Years)
Pediatric Dosing
In children and adolescents, the dose depends on age and body weight and will be individually adjusted by your doctor. At the start of treatment, the dose typically ranges from 400 to 1,000 mg daily. Growing children require particularly careful monitoring, as their copper needs change as they develop. Your doctor will regularly reassess the dose and adjust it based on copper levels and clinical response.
How to Take Cufence
Proper administration of Cufence is essential for the medication to work effectively. The following points are critically important:
- Swallow capsules whole with water. Do not open, crush, or chew the capsules.
- Take on an empty stomach – at least 1 hour before meals or 2 hours after meals.
- Take with water only. Do not take with milk, juice, or any other beverage, as these can reduce the drug's effectiveness.
- Avoid eating or drinking (except water) for 2 hours before and 1 hour after taking Cufence.
- Divide the total daily dose into 2 to 4 smaller doses as instructed by your doctor.
- Contact your doctor if you have difficulty swallowing the capsules.
| Patient Group | Daily Dose Range | Dosing Frequency | Key Considerations |
|---|---|---|---|
| Adults | 800–1,600 mg/day | 2–4 divided doses | Higher doses during initial de-coppering phase; reduce during maintenance |
| Elderly | 800–1,600 mg/day | 2–4 divided doses | Same as adult dose; monitor renal function |
| Adolescents (12–17 years) | 400–1,000 mg/day | 2–4 divided doses | Dose based on body weight; frequent monitoring during growth |
| Children (5–11 years) | 400–1,000 mg/day | 2–4 divided doses | Individualized by weight; regular dose adjustments as child grows |
Missed Dose
If you forget to take a dose, take the next dose at the usual scheduled time. Do not take a double dose to make up for a missed dose. Missing occasional doses is unlikely to cause immediate problems, but regular adherence to your medication schedule is essential for maintaining adequate copper control. If you frequently forget doses, speak with your doctor or pharmacist about strategies to help you remember, such as setting alarms or using a pill organizer.
Overdose
If you take more Cufence than prescribed, you may experience nausea, vomiting, and dizziness. Contact your doctor or seek medical attention immediately. In cases of significant overdose, medical monitoring may be necessary to assess for signs of copper depletion and to provide appropriate supportive care. There is no specific antidote for trientine overdose; treatment is symptomatic and supportive.
Cufence is intended for long-term use because Wilson's disease is a lifelong condition. Do not stop or change your treatment without talking to your doctor, even if you feel well. Untreated Wilson's disease is fatal, and stopping chelation therapy can lead to rapid copper re-accumulation with potentially devastating consequences, including acute liver failure and severe neurological deterioration.
What Are the Side Effects of Cufence?
Like all medicines, Cufence can cause side effects, although not everybody gets them. Most side effects are mild to moderate and may improve as your body adjusts to the medication. However, some side effects can be serious and require immediate medical attention.
It is important to distinguish between side effects of the medication itself and symptoms that may result from changes in copper levels during treatment. At the start of therapy, mobilization of copper from tissue stores can temporarily worsen neurological symptoms. Conversely, excessive chelation over time can cause copper deficiency, which has its own set of symptoms including fatigue, weakness, and blood count abnormalities.
Contact your doctor immediately if you experience any of the following: severe abdominal pain, persistent diarrhea, tremors, loss of coordination, slurred speech, muscle stiffness, or worsening muscle spasms. These may indicate serious complications that require prompt medical evaluation.
Common
May affect up to 1 in 10 people
- Nausea (especially at the start of treatment)
Uncommon
May affect up to 1 in 100 people
- Skin rash
- Anemia (you may feel unusually tired or weak)
Not Known
Frequency cannot be estimated from available data
- Inflammation of the small intestine (duodenitis) – may cause upper abdominal pain, nausea, and bloating
- Inflammation of the large intestine (colitis) – may cause severe abdominal pain, persistent diarrhea, and rectal bleeding
- Neurological symptoms (tremors, loss of coordination, slurred speech, muscle stiffness, worsening muscle spasms) – particularly at the start of treatment
Managing Side Effects
Nausea is the most frequently reported side effect and tends to occur at the beginning of treatment. It often improves as the body adjusts to the medication over the first few weeks. Taking Cufence with a small amount of water and remaining upright for at least 30 minutes after taking the capsules may help reduce nausea. If nausea persists or is severe, your doctor may adjust the dosing schedule or explore other management strategies.
Anemia associated with trientine may occur due to the chelation of iron or, in rare cases, due to excessive copper removal leading to copper-deficiency anemia. Your doctor will monitor your blood counts regularly to detect any changes early. If anemia develops, iron supplementation may be considered, though the timing must be carefully managed to avoid interaction with trientine (at least 2 hours apart).
Skin rashes should be reported to your doctor, who will evaluate whether they are related to Cufence or have another cause. In some patients who have switched from D-penicillamine to trientine, skin reactions may be related to the prior medication rather than to trientine itself.
If you experience any side effects not listed here, or if any of the listed side effects become bothersome or do not improve, inform your doctor or pharmacist. Reporting suspected side effects helps regulatory authorities continuously monitor the benefit-risk balance of the medicine. You can report side effects through your national medicines agency or directly to the European Medicines Agency.
How Should You Store Cufence?
Proper storage of Cufence is essential to maintain the effectiveness and safety of the medication. Trientine capsules are sensitive to moisture and must be protected from humid conditions. The following storage guidelines should be observed:
- Keep out of reach of children. Store this medicine where children cannot see or access it.
- Check the expiry date. Do not use Cufence after the expiry date stated on the bottle label and outer carton. The expiry date refers to the last day of that month.
- Use within 3 months of first opening the bottle. The moisture-sensitive nature of the capsules means that prolonged exposure to air and humidity can degrade the medication.
- Close the bottle tightly after each use. The bottle contains a silica gel desiccant sachet to absorb moisture – leave this sachet in the bottle and do not swallow it.
- Do not use if the capsules become sticky or wet. Moisture exposure can affect the integrity of the capsules and the stability of the active ingredient.
- Dispose properly. Do not throw away medicines via household waste or wastewater. Ask your pharmacist how to dispose of medicines you no longer use. These measures help protect the environment.
The Cufence 100 mg capsules come in a white, opaque HDPE bottle with a child-resistant HDPE screw cap and heat seal. Each bottle contains 200 hard capsules. The capsules are white, oval, size 3 (15.8 mm × 5.85 mm) with "Cufence 100" printed in grey ink.
The Cufence 200 mg capsules come in a brown glass bottle with a polypropylene lid and heat seal. Each bottle contains 100 hard capsules. The capsules are white, oval, size 0 (21.8 mm × 7.66 mm) with "Cufence" printed in grey ink.
What Does Cufence Contain?
Understanding the composition of your medication can be important, particularly if you have allergies or sensitivities to specific excipients. Below is a detailed breakdown of the active and inactive ingredients in Cufence capsules.
Active Ingredient
The active substance in Cufence is trientine (triethylenetetramine), provided as trientine dihydrochloride salt. It is important to note that the strength listed on the packaging refers to the amount of free trientine base, not the total salt weight:
- Cufence 100 mg: Each capsule contains 150 mg trientine dihydrochloride, equivalent to 100 mg trientine.
- Cufence 200 mg: Each capsule contains 300 mg trientine dihydrochloride, equivalent to 200 mg trientine.
Inactive Ingredients (Excipients)
| Component | Ingredients | Purpose |
|---|---|---|
| Capsule contents | Magnesium stearate, colloidal anhydrous silica | Lubricant and flow agent to ensure uniform capsule filling |
| Capsule shell | Gelatin, titanium dioxide (E171) | Forms the capsule shell; titanium dioxide provides white opacity |
| Printing ink | Shellac, propylene glycol (E1520), titanium dioxide (E171), black iron oxide (E172), yellow iron oxide (E172) | Used for product identification text printed on capsule surface |
The marketing authorization holder for Cufence is Univar Solutions BV (Schouwburgplein 30, 3012 CL Rotterdam, Netherlands), and the manufacturer is Aesica Pharmaceuticals GmbH (Alfred-Nobel Strasse 10, 40789 Monheim, Germany). Additional information about Cufence is available on the European Medicines Agency website.
Frequently Asked Questions About Cufence
Wilson's disease is a rare inherited (autosomal recessive) genetic disorder caused by mutations in the ATP7B gene, which encodes a copper-transporting protein in the liver. When this protein is defective, the body cannot properly eliminate copper through bile, leading to its progressive accumulation in the liver, brain, cornea (Kayser-Fleischer rings), kidneys, and other organs. Because the genetic defect is permanent, the body will always have difficulty excreting copper, meaning treatment must continue for life to prevent re-accumulation and organ damage. Without treatment, Wilson's disease is fatal. With consistent treatment, however, patients can lead normal, healthy lives.
Both Cufence and Cuprior contain trientine as their active ingredient and are used to treat Wilson's disease. Cufence contains trientine dihydrochloride and is available as hard capsules in 100 mg and 200 mg strengths. Cuprior contains trientine tetrahydrochloride and is available as film-coated tablets. The key differences lie in the salt form and formulation. The two products may have slightly different dosing requirements due to the different salt forms. Your doctor will prescribe the appropriate product and dose for your situation. Do not switch between products without medical guidance, as dose adjustments may be necessary.
While Cufence helps remove excess copper from your body, it is advisable to limit your intake of copper-rich foods to reduce the burden on your chelation therapy. Foods particularly high in copper include liver and organ meats, shellfish (especially oysters, lobster, and crab), nuts (especially cashews and almonds), chocolate and cocoa products, mushrooms, dried fruits, seeds, and soy products. Drinking water from copper pipes may also contribute to copper intake. Your doctor or a dietitian can help you develop a dietary plan that minimizes copper intake while maintaining proper nutrition.
Trientine is unlikely to have any effect on the ability to drive or operate machinery. There are no known pharmacological effects of the drug that would impair cognitive function, reaction time, or motor skills. However, if you experience neurological symptoms (particularly at the start of treatment), such as dizziness, tremors, or coordination problems, you should exercise caution and consult your doctor before driving or operating potentially dangerous machinery.
Stopping Cufence without medical supervision is extremely dangerous. Without ongoing copper chelation, copper will rapidly re-accumulate in your tissues, particularly the liver and brain. This can lead to acute liver failure (which may be life-threatening and require emergency liver transplantation), severe neurological deterioration (worsening tremors, speech difficulties, movement disorders, psychiatric symptoms), kidney damage, and hemolytic anemia. Even if you feel well and your symptoms are controlled, this simply means the treatment is working – it does not mean you no longer need it. Never stop or reduce your dose without consulting your specialist physician.
Your response to Cufence is monitored through a combination of clinical assessments and laboratory tests. Key monitoring parameters include 24-hour urinary copper excretion (to assess whether copper is being adequately removed), serum free (non-ceruloplasmin-bound) copper levels, liver function tests, full blood count (to detect anemia), neurological examination, and slit-lamp eye examination (to monitor Kayser-Fleischer rings). Monitoring is more frequent at the start of treatment and during dose adjustments, typically every 1–3 months initially, and may become less frequent (every 6–12 months) once stable maintenance is achieved.
References
- European Medicines Agency. Cufence (trientine dihydrochloride) – Summary of Product Characteristics. EMA/2024. Available at: www.ema.europa.eu/en/medicines/human/EPAR/cufence
- European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: Wilson’s disease. Journal of Hepatology. 2012;56(3):671–685. doi:10.1016/j.jhep.2011.11.007
- Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2023;77(4):1428–1455. doi:10.1002/hep.32801
- Weiss KH, Stremmel W. Clinical considerations for an effective medical therapy in Wilson’s disease. Annals of the New York Academy of Sciences. 2014;1315(1):81–85. doi:10.1111/nyas.12529
- Członkowska A, Litwin T, Dusek P, et al. Wilson disease. Nature Reviews Disease Primers. 2018;4(1):21. doi:10.1038/s41572-018-0018-3
- Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089–2111. doi:10.1002/hep.22261
- World Health Organization. WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
- Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. The Lancet. 1982;319(8273):643–647. doi:10.1016/S0140-6736(82)92201-2
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in hepatology, clinical pharmacology, and rare diseases.
Medical Content
Written by iMedic Medical Writers with expertise in hepatology and clinical pharmacology
Medical Review
Reviewed by iMedic Medical Review Board according to EASL, AASLD, and EMA guidelines
Fact Checking
All medical claims verified against peer-reviewed sources and official prescribing information
Accessibility
WCAG 2.2 Level AAA compliance verified. Content optimized for screen readers and assistive technology
Evidence standard: All medical information on this page is based on evidence level 1A (systematic reviews and meta-analyses of randomized controlled trials) and official regulatory documentation (EMA SmPC, AASLD/EASL guidelines). No commercial funding or pharmaceutical sponsorship.
Last reviewed: | Published: