CUPRIPEN 250 mg CAPSULES

2. What you need to know before you take Cupripen

Do not take Cupripen

• if you are allergic to penicillamine or any of the other ingredients of this medicine (listed in section 6),
• if you are allergic to penicillins,
• if you have had any liver, kidney, or severe blood diseases when taking penicillamine,
• if you have a disease called systemic lupus erythematosus
• if you are taking gold salts, antimalarials, cytotoxics, oxyphenbutazone, or phenylbutazone.

Do not take Cupripen if you have any of the above conditions. If you are not sure, talk to your doctor or pharmacist before taking Cupripen, as this medicine may worsen these problems.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Cupripen if:

• you are elderly
• you are going to have or have had surgery.
• you have glucose-6-phosphate dehydrogenase deficiency
• you have liver or kidney problems
• if you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine (see section "Pregnancy, breastfeeding, and fertility").

Before starting treatment, tell your doctor or pharmacist if you have any of the conditions mentioned above. Your doctor will want to monitor the effect of the medicine on you.

Special precautions for treatment with Cupripen:

Penicillamine may cause serious birth defects. You should avoid becoming pregnant while using Cupripen and for at least six months and five days after finishing treatment. See also section "Pregnancy, breastfeeding, and fertility".

Recommended follow-up tests and safety measures:

Even when Cupripen is administered at low doses, severe side effects can occur. To detect them in time, your doctor will need to perform blood tests and check-ups.

Before starting treatment with Cupripen:

You will have blood tests and urine tests. If you have any liver or kidney disease, you will have tests to check liver and kidney function.

During treatment:

You will have the following tests, at least once a week for the first two months of treatment and then every month:

• blood tests
• urine tests

Maintain the frequency of intakes that your doctor has indicated to avoid the appearance of poor tolerance symptoms.

In prolonged treatments, your doctor may prescribe pyridoxine (Vitamin B6).

Other medicines and Cupripen

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

If you are taking other medicines, penicillamine may affect their mechanism of action or cause side effects. Therefore, it may be necessary to change the dose of the medicine or suspend treatment together. If you take any of the following medicines, consult your doctor or pharmacist before taking Cupripen:

• Aluminum or magnesium salts (medicines used to treat heartburn)
• Digoxin (a medicine used to treat heart diseases)
• Indomethacin (a medicine used to treat pain)
• Isoniazid (a medicine used to treat tuberculosis)
• Levodopa (a medicine used to treat Parkinson's disease)
• Iron salts (medicines used to treat low iron levels or anemia)
• Gold salts (a medicine used to treat rheumatism)
• Phenylbutazone or oxyphenbutazone (medicines used to treat pain and inflammation)
• Antimalarials (medicines used to treat malaria)
• Cytotoxics (medicines used to treat cancer)

If you are unsure whether any of the medicines you are taking are included in the above list, ask your doctor or pharmacist before taking Cupripen.

Taking Cupripen with food and drinks

Take preferably on an empty stomach, 1 hour before or 2 hours after meals, as food interferes with its absorption.

The capsules should be swallowed whole with water.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

The use of Cupripen is not recommended during pregnancy. Inform your doctor if you are pregnant or trying to become pregnant. Your doctor will decide if you can take Cupripen during that time.

Breastfeeding

It is not known whether Cupripen passes into breast milk. For this reason, its administration is not recommended during the breastfeeding period. Your doctor will decide if you can take Cupripen during this time.

Male fertility

Penicillamine may be genotoxic, which means it can cause genetic mutations. Therefore, you should avoid fathering a child or donating sperm while taking Cupripen and for at least three months and five days after stopping treatment.

Driving and using machines

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

3. How to take Cupripen

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Method of administration

Cupripen is for oral use.

The capsules should be swallowed whole, with a glass of water, on an empty stomach, at least 1 hour before or 2 hours after meals.

Dose

Your doctor will establish the suitable dose for you and make the necessary adjustments, as the dosage must be individualized.

Wilson's disease

Adults

Your doctor will indicate how many capsules you should take per day. The usual dose is 6 to 8 capsules per day. Once you feel better, your doctor may reduce the dose to 3 to 4 capsules per day. It is not recommended to take 8 capsules per day for more than 12 months.

Use in elderly patients

Your doctor will indicate how many capsules you should take and how often during the day. The dose will depend on your weight. The usual dose is 20 mg of penicillamine per day per kilogram of weight. Your doctor will adjust the dose to the minimum necessary to control your disease.

Use in adolescents (12 to < 18 years)

Your doctor will indicate how many capsules you should take per day. The usual dose is 3 to 4 capsules per day.

Use in children (5 to < 12 years)

Your doctor will indicate how many capsules the child should take and how often during the day. The dose will depend on the child's weight. The usual dose is 20 mg of penicillamine per day per kilogram of weight, divided into two or three doses taken 1 hour before meals.

Patients with renal insufficiency

In patients with renal impairment, special precautions should be taken to control side effects.

Heavy metal poisoning

Adults (including elderly patients)

Your doctor will indicate how many capsules you should take per day. The dose is 4 to 6 capsules per day until your doctor indicates that the amount of heavy metals in your urine is normal. If treatment is prolonged, the dose should not exceed 40 mg per day per kilogram of weight.

Use in children and adolescents (5 to < 18 years)

Your doctor will indicate how many capsules you should take per day. The dose will depend on the child's weight. The usual dose is 20 to 25 mg per day per kilogram of weight. If necessary, a dose of 100 mg of penicillamine per day per kilogram of weight may be administered, up to a maximum dose of 1,050 mg of penicillamine per day per kilogram of weight.

Cystinuria

The dose must be adjusted individually, taking into account the amount of cystine excreted in the urine.

Adults

If you are taking Cupripen to dissolve cystine stones, the dose is 4 to 12 capsules per day, divided into several doses. If you are taking Cupripen to prevent the formation of cystine stones, the dose will be 2 to 4 capsules per day before bedtime; in this case, you should drink at least 3 liters of fluids per day.

Use in elderly patients

Your doctor will determine the suitable dose for you, which should be the minimum necessary to keep cystine levels below 200 mg per liter of urine.

Use in children and adolescents (5 to < 18 years)

The dose will depend on the child's weight. The usual dose is 20 to 30 mg per day per kilogram of weight, in two or three divided doses taken 1 hour before meals. Your doctor may change the dose depending on the results of the child's urine tests.

Patients with renal insufficiency

In patients with renal impairment at the start of treatment, lower initial doses should be administered. Maintenance doses should be reviewed at least every 4 weeks.

If you take more Cupripen than you should

If you take more Cupripen than you should, consult your doctor immediately.

If you forget to take Cupripen

Do not take a double dose to make up for forgotten doses.

If you stop taking Cupripen

Do not stop or change treatment without talking to your doctor, even if you feel better. If you have forgotten to take several doses, consult your doctor to indicate the dosage schedule to follow until you reach your maintenance dose.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency and severity of side effects will depend on the dose and frequency of administration. It is important that your doctor performs periodic checks, as serious side effects can occur even with the lowest doses. Your doctor will perform tests to control abnormalities that occur in the blood and changes in the kidneys and liver.

Common (may affect up to 1 in 10 people)

• nausea, loss of taste, bad taste, loss of appetite, and vomiting.
• skin rashes
• redness of the skin (erythema)
• itching
• proteins in your urine (detected with a urine test)

Uncommon (may affect up to 1 in 100 people)

• ringing in the ears
• vision loss
• muscle weakness, joint pain (arthralgia)
• excessive elimination of proteins in the urine (nephrotic syndrome)
• inflammatory kidney disease (membranous glomerulonephritis)

Rare (may affect up to 1 in 1,000 people)

• diarrhea
• decrease in the number of blood cells (anemia, leukopenia, thrombocytopenia)
• mouth ulcers
• hair loss
• inflammation of the lung tissue (pneumonitis)
• bronchiolitis
• yellowish discoloration of the nails (yellow nail syndrome)
• inflammatory disease that causes muscle weakness (polymyositis)
• breast enlargement

Not known (cannot be estimated from the available data)

• pseudoxanthoma elasticum (a disease of the connective tissue)
• perforating elastosis (a skin disease)
• systemic lupus erythematosus (an allergic condition that causes joint pain, skin rashes, and fever)
• myasthenia gravis (a disease that causes muscle weakness)

Reporting of side effects

If you experience any side effects, talk to your doctor, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website (http://www.aemps.gob.es/). By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Cupripen

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

Store in the original packaging to protect from moisture.

Do not use this medicine after the expiry date stated on the packaging. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to a pharmacy. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and further information

Composition of Cupripen 250 mg hard capsules:

• The active substance is penicillamine. Each hard capsule of Cupripen contains 250 mg of penicillamine.
• The other ingredients are:

Contents of the capsules: Magnesium stearate; Capsule shell: Gelatin, Titanium dioxide (E171), Quinoline yellow (E104).

Appearance and packaging of the product

Cupripen 250 mg hard capsules:

Cupripen are hard gelatin capsules, oblong, white and yellow in color.

They are available in a pack containing 30 capsules.

Marketing authorization holder and manufacturer

Laboratorios Rubió, S. A.

C/ Industria, 29

Polígono Industrial Comte de Sert

08755 Castellbisbal – Barcelona

Spain

Date of last revision of this leaflet:10/2023.

Detailed information on this medicine is available on the website of the Spanish Medicines and Healthcare Products Agency (AEMPS) (http://www.aemps.gob.es/).