Package Insert: Information for the Patient

Cufence 100 mg Hard Capsules

Cufence 200 mg Hard Capsules

Trientine

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you must not give it to other peopleeven if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

Cufence is indicated for the treatment of Wilson's disease in adults, adolescents, and children 5 years of age or older. It is used in patients who cannot take another medication, D-penicillamine, due to adverse effects.

Cufence contains the active ingredient trientine, a copper chelating agent that is used to eliminate excess copper from the body. Cufence binds to copper, which is then expelled from the body.

Do not take Cufence

If you are allergic to trientine or any of the other components of this medication (listed in section 6).

The signs of an allergic reaction include, among others, skin rash, itching, facial swelling, dizziness, and breathing difficulties.

Warnings and precautions

Your doctor will need to regularly check your disease symptoms and copper levels in your blood and urine. Regular monitoring is especially important at the beginning of treatment or when changing doses, in growing children and pregnant women, to ensure that copper levels remain at a suitable level. Your doctor may need to increase or decrease the dose of Cufence.

Problems in the nervous system (such as tremors, lack of coordination, difficulty speaking, muscle stiffness, and worsening muscle spasms) may occur, especially in patients who have just started taking Cufence. If you notice any of them while taking Cufence, you must inform your doctor immediately.

Pseudolupus-like reactions (symptoms may include persistent skin rash, fever, joint pain, and fatigue) have been described in some patients who have switched to trientine after taking penicillamine. However, it has not been possible to determine whether the reaction was due to trientine or the previous treatment with penicillamine.

Other medications and Cufence

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

If you are taking iron tablets or medications that neutralize stomach acid, leave at least 2 hours before or after taking Cufence, as they may reduce its effect. It is recommended to take trientine at least 1 hour before or after any other medication.

Taking Cufence with food and drinks

Take this medication only with water. Do not take it with other beverages, milk, or food, as they may reduce the effect of the medication. Avoid eating or drinking (except water) for 2 hours before and 1 hour after taking the medication.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication. It is very important to continue treatment to maintain normal copper levels during pregnancy. You must discuss the possible benefits of treatment with your doctor, taking into account the potential risks. Your doctor will advise you on the best treatment and dosage for your situation. If you become pregnant while taking Cufence, talk to your doctor.

If you are pregnant and taking Cufence, you will have regular checks throughout pregnancy to detect any effects on the baby or changes in your copper levels.

The limited available information indicates that Cufence is not excreted in breast milk, but there is no certainty that the baby is at no risk. It is essential to inform your doctor if you are breastfeeding or plan to do so. Your doctor will help you decide whether to stop breastfeeding or stop taking Cufence, considering the benefits of breastfeeding for the baby and the benefits of Cufence for the mother. Your doctor will advise you on the best treatment and dosage for your situation.

Driving and operating machinery

Cufence is unlikely to affect your ability to drive or use tools or machines.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Adults (including elderly patients)

The usual dose is between 800 and 1,600 mg per day, taken orally.

Use in children and adolescents (5 to 17 years old)

The dose in children and adolescents depends on age and body weight, and will be adjusted by your doctor. Initially, the dose varies between 400 and 1,000 mg per day.

Administration form

Your doctor will decide what is the correct dose for you.

The total daily dose may be divided into 2 to 4 smaller doses, as indicated by your doctor. Swallow the capsules whole with water, with an empty stomach, at least 1 hour before or 2 hours after meals.

Patients who have difficulty swallowing should contact their doctor.

If you take more Cufence than you should

If you take more medication than you should, you may experience nausea, vomiting, and dizziness. You should contact your doctor or another healthcare professional immediately.

If you forget to take Cufence

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 the missed dose.

If you interrupt treatment with Cufence

This medication is indicated for long-term use because Wilson's disease is a lifelong condition. Do not suspend or change treatment without consulting your doctor, even if you feel better.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

At times (frequency unknown; cannot be estimated from available data) treatment with this medication may produce inflammation of the small intestine or colon. If you experience any of the following side effects, contact your doctorimmediately:

• Severe stomach pain
• Persistent diarrhea
• Nervous system problems (for example, tremor, lack of coordination, difficulty speaking, muscle stiffness, worsening muscle spasms)

Other side effects may include:

Frequent (may affect up to 1 in 10 patients)

• Nausea (especially when starting treatment)

Rare (may affect up to 1 in 100 patients)

• Skin eruptions
• Anemia (may feel unusually tired)

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can alsoreport them directly through thenational notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the outer packaging after CAD. The expiration date is the last day of the month indicated.

Use within 3 months after the first opening of the bottle. Keep the bottle perfectly closed to protect it from moisture. Do not use if the capsules become sticky or wet.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Cufence

The active ingredient is trientine.

• Cufence 100 mg hard capsules contain 150 mg of trientine dihydrochloride, equivalent to 100 mg of trientine.
• Cufence 200 mg hard capsules contain 300 mg of trientine dihydrochloride, equivalent to 200 mg of trientine.

The other components are:

• Capule content: magnesium stearate and anhydrous colloidal silica
• Capule coating: gelatin and titanium dioxide (E171)
• Printing ink: shellac, propylene glycol (E1520), titanium dioxide (E171), iron oxide black (E172), and iron oxide yellow (E172)

Appearance of the product and contents of the packaging

Cufence 100 mg, hard capsules

HDPE opaque white bottle with a child-resistant HDPE screw cap and induction-sealed with a dry silica gel desiccant. Each hard capsule is white, oval-shaped, size 3 (15.8 mm x 5.85 mm), and printed with "Cufence" in grey ink.

Package size: a bottle of 200 hard capsules

Cufence 200 mg, hard capsules

Amber glass bottle with a polypropylene cap and induction-sealed with a desiccant containing dry silica gel. Each capsule is white, oval-shaped, size 0 (21.8 mm x 7.66 mm), and printed with "Cufence" in grey ink.

Package size: a bottle of 100 hard capsules.

Only some package sizes may be commercially available.

Marketing Authorization Holder

Univar Solutions BV

Schouwburgplein 30

3012 CL Rotterdam

Netherlands

Responsible Person for Manufacturing

Aesica Pharmaceuticals GmbH

Alfred-Nobel Strasse 10

40789 Monheim

Germany

Last review date of this leaflet: {MM/AAAA}

Other sources of information

The detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu . There are also links to other websites on rare diseases and orphan medicines.