PROCYSBI 25 mg HARD GASTRO-RESISTANT CAPSULES

Introduction

Package Leaflet: Information for the User

PROCYSBI 25 mg gastro-resistant hard capsules

PROCYSBI 75 mg gastro-resistant hard capsules

cysteamine (mercaptamine bitartrate)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

if they have the same symptoms as you.

• If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. See section 4.

Contents of the pack

1. What is PROCYSBI and what is it used for
2. What you need to know before you take PROCYSBI
3. How to take PROCYSBI
4. Possible side effects
5. Storage of PROCYSBI
6. Contents of the pack and further information

1. What is PROCYSBI and what is it used for

PROCYSBI contains the active substance cysteamine (also known as mercaptamine) and is taken for the treatment of nephropathic cystinosis in children and adults. Cystinosis is a disease that affects the body's functioning, with an abnormal accumulation of the amino acid cystine in various organs such as the kidneys, eyes, muscles, pancreas, and brain. The accumulation of cystine causes kidney damage and the elimination of excessive amounts of glucose, proteins, and electrolytes. At different ages, different organs may be affected.

PROCYSBI is a medicine that reacts with cystine and decreases its levels in cells. To get the most benefit, cysteamine therapy should be started quickly after confirmation of the diagnosis of cystinosis.

2. What you need to know before you take PROCYSBI

Do not take PROCYSBI

• If you are allergic to cysteamine (also known as mercaptamine) or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to penicillamine (not "penicillin", but a medicine used to treat Wilson's disease).
• If you are breast-feeding.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking PROCYSBI.

• Since oral cysteamine does not prevent the accumulation of cystine crystals in the eyes, you should continue to use the cysteamine eye drops prescribed by your doctor.
• Whole cysteamine capsules should not be given to children under 6 years of age due to the risk of choking (see section 3 "How to take PROCYSBI - Method of administration").

• Severe skin lesions can occur in patients treated with high doses of cysteamine. Your doctor will perform periodic skin and bone examinations and reduce or discontinue treatment if necessary (see section 4).

• Ulcers and stomach and intestinal bleeding can occur in patients treated with cysteamine (see section 4).
• During treatment with cysteamine, other gastrointestinal symptoms may occur, particularly nausea, vomiting, loss of appetite, and stomach pain. In these cases, your doctor may interrupt and modify the dose.
• Talk to your doctor if you experience unusual stomach symptoms or changes in stomach symptoms.
• During treatment with cysteamine, symptoms such as seizures, fatigue, drowsiness, depression, and brain disorders (encephalopathy) may occur. If you experience these symptoms, notify your doctor, who will adjust the dose.
• During treatment with cysteamine, abnormalities in liver function or a decrease in the number of white blood cells (leukopenia) may occur. Your doctor will periodically monitor blood counts and liver function.
• Your doctor will periodically monitor the appearance of benign intracranial hypertension (or pseudotumor cerebri [PTC]) and optic nerve inflammation (papilledema) associated with cysteamine treatment. You will undergo periodic eye examinations to identify this disorder, as immediate treatment can prevent vision loss.

Other medicines and PROCYSBI

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. If your doctor prescribes bicarbonate, do not take it at the same time as PROCYSBI; take it at least one hour before or one hour after taking the medicine.

Taking PROCYSBI with food and drinks

For at least 1 hour before and 1 hour after taking PROCYSBI, try to avoid fatty or protein-rich foods, as well as any food or liquid that may reduce stomach acidity, such as milk or yogurt. If this is not possible, you can eat a small amount (approximately 100 grams) of food (preferably carbohydrates, e.g., bread, pasta, fruits) during the hour before and after administration of PROCYSBI. Take the capsule with an acidic drink (such as orange juice or any other acidic juice) or water. For children and patients with swallowing problems, see section 3 "How to take PROCYSBI - Method of administration".

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not use this medicine if you are pregnant, especially during the first trimester. Before starting treatment, you must have a pregnancy test with a negative result, while during treatment, you must use an appropriate contraceptive method. If you are a woman and plan to become pregnant, consult your doctor about stopping treatment with this medicine, as it may be harmful to the fetus.

Do not use this medicine during breast-feeding (see section 2 "Do not take PROCYSBI").

Driving and using machines

This medicine may cause drowsiness. When starting treatment, avoid driving, using machines, or performing other hazardous activities until you know how it affects you.

PROCYSBI contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to take PROCYSBI

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

The recommended dose for you or your child will depend on their age and weight. The expected maintenance dose is 1.3 g/m2/day.

Dosing regimen

Take this medicine twice a day, every 12 hours. To get the most benefit from this medicine, try to avoid food and dairy products for at least the hour before and after taking PROCYSBI. If this is not possible, you can eat a small amount (approximately 100 grams) of food (preferably carbohydrates, e.g., bread, pasta, fruits) during the hour before and after administration of PROCYSBI.

It is important that you take PROCYSBI consistently over time.

Do not increase or decrease the amount of medicine without your doctor's prior approval.

The total daily dose should not exceed 1.95 g/m2/day.

Duration of treatment

Treatment with PROCYSBI should continue for life, as indicated by your doctor.

Method of administration

It is taken orally (by mouth) only.

For this medicine to work properly:

• For patients who can swallow the capsule whole:

Swallow the capsule whole with an acidic drink (such as orange juice or any other acidic juice) or water. Do not crush or chew the capsules or the contents of the capsules. Children under 6 years of age may not be able to swallow the hard gastro-resistant capsules and may choke on them. You can give Procysbi to children under 6 years of age by opening the capsules and sprinkling the contents over food or liquids, as instructed below.

• For patients who cannot swallow the capsule whole or use a feeding tube:

Sprinkle over food

Open the hard gastro-resistant capsules and sprinkle the contents (granules) over approximately 100 grams of food, such as apple sauce or fruit jam.

Gently mix the granules into the soft food, creating a mixture of granules and food. Consume the entire mixture. Then, drink approximately 250 ml of an acidic drink (such as orange juice or any other acidic fruit juice) or water to facilitate ingestion of the mixture.

If you do not consume the mixture immediately, you can refrigerate it (between 2°C and 8°C) from preparation to administration time and take it within 2 hours of preparation. Do not store any of the mixture after 2 hours.

Administration through a feeding tube

Open the hard gastro-resistant capsules and sprinkle the contents (granules) over approximately 100 grams of apple sauce or fruit jam. Gently mix the granules into the soft food, creating a mixture of granules and soft food. Administer the mixture through the gastrostomy tube, nasogastric tube, or gastrostomy-jejunostomy tube using a catheter-tip syringe. Before administering PROCYSBI, open the button on the gastrostomy tube and attach the feeding tube. Flush with 5 ml of water to rinse the button. Aspirate the mixture into the syringe. A maximum mixture volume of 60 ml in a catheter-tip syringe for a straight or bolus feeding tube is recommended. Place the opening of the syringe containing the PROCYSBI and food mixture into the feeding tube and fill it completely with the mixture: gently pressing the syringe and keeping the feeding tube in a horizontal position during administration may help prevent clogging problems. It is suggested to use a viscous food such as apple sauce or fruit jam at a rate of about 10 ml every 10 seconds until the syringe is completely empty, to avoid clogging. Repeat the above step until all of the mixture is administered. After administration of PROCYSBI, aspirate 10 ml of fruit juice or water into another syringe and flush the gastrostomy tube, making sure that no mixture of PROCYSBI and food is left in the gastrostomy tube.

If you do not consume the mixture immediately, you can refrigerate it (between 2°C and 8°C) from preparation to administration time and consume it within 2 hours of preparation. Do not store any of the mixture after 2 hours.

Consult your child's doctor for complete instructions on how to administer the product through feeding tubes or if you have problems with tube clogging.

Sprinkle in orange juice or any other acidic fruit juice or water

Open the hard gastro-resistant capsules and sprinkle the contents (granules) into approximately 100 to 150 ml of acidic fruit juice (such as orange juice or any other acidic fruit juice) or water. Gently mix the drinkable PROCYSBI mixture for 5 minutes, mixing it in a cup or shaking it in a covered cup (e.g., a "sipping" cup), and drink the mixture.

If you do not take the mixture immediately, you can refrigerate it (between 2°C and 8°C) from preparation to administration time and take it within 30 minutes of preparation. Do not store any of the mixture after 30 minutes.

Administration of a drinkable mixture with an oral syringe

Aspirate the drinkable mixture into a dosing syringe and administer it directly into the mouth.

If you do not consume the mixture immediately, you can refrigerate it (between 2°C and 8°C) from preparation to administration time and consume it within 30 minutes of preparation. Do not store any of the mixture after 30 minutes.

Your doctor may recommend or prescribe the inclusion, in addition to cysteamine, of one or more supplements to replace important electrolytes lost by the kidneys. It is essential that these supplements are taken exactly as instructed. If you forget several doses of the supplements or experience weakness or drowsiness, consult your doctor for instructions to follow.

Regular blood tests are necessary to measure the amount of cystine in white blood cells and/or the concentration of cysteamine in the blood to help determine the correct dose of PROCYSBI. You or your doctor will arrange for these blood tests to be performed. These tests should be performed 12.5 hours after the previous night's dose and 30 minutes after the morning dose. Periodic blood and urine tests are also necessary to measure the levels of important electrolytes to help your doctor or you adjust the doses of these supplements correctly.

If you take more PROCYSBI than you should

If you have taken more PROCYSBI than prescribed, talk to your doctor immediately or go to the emergency department of a hospital. You may experience drowsiness.

If you forget to take PROCYSBI

If you have missed a dose, take it as soon as possible. If it is less than 4 hours until the next dose, skip the missed dose and return to the normal schedule.

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

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

4. Possible side effects

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

Seek immediate medical attention if you notice any of the following side effects, you may need urgent medical treatment:

• Severe allergic reactions (uncommon): go to the emergency department if you have any of the following signs of an allergic reaction: hives, difficulty breathing, swelling of the face, lips, tongue, or throat.

If you experience any of the following side effects, contact your doctor immediately. Since some of these side effects are serious, ask your doctor to explain the warning signs.

Common side effects(may affect up to 1 in 10 people):

• Skin rash: inform your doctor immediately. It may be necessary to temporarily discontinue treatment with PROCYSBI until the rash disappears. If the rash is severe, your doctor may withdraw treatment with cysteamine.
• Abnormalities in liver function in blood tests. Your doctor will monitor this effect.

Uncommon side effects(may affect up to 1 in 100 people):

• Skin lesions, bone lesions, and joint problems: treatment with high doses of cysteamine can cause skin lesions. These include skin stretch marks, bone lesions (such as fractures), bone deformities, and joint problems. Examine your skin while taking this medicine. Notify any changes to your doctor. Your doctor will monitor these problems.

• Low white blood cell count. Your doctor will monitor this effect.
• Central nervous system symptoms: some patients taking cysteamine have experienced seizures, depression, and excessive sleepiness (somnolence). Notify your doctor if you experience these symptoms.
• Gastrointestinal problems: patients taking cysteamine have developed ulcers and bleeding. Notify your doctor immediately if you experience stomach pain or vomit blood.
• Benign intracranial hypertension, also known as pseudotumor cerebri, has also been reported with the use of cysteamine. This is a disorder characterized by increased pressure of the fluid surrounding the brain. Inform your doctor immediately if you experience any of the following symptoms while taking PROCYSBI: ringing in the ears, dizziness, double vision, blurred vision, loss of vision, pain in the back of the eye, or pain when moving it. Your doctor will perform eye examinations to describe and treat this problem in its early stages, which will help reduce the likelihood of vision loss.

The following side effects are also reported with an estimated frequency of occurrence with PROCYSBI.

Very common side effects(may affect more than 1 in 10 people):

• nausea
• vomiting
• loss of appetite
• diarrhea
• fever
• drowsiness

Common side effects:

• headache
• encephalopathy
• abdominal pain
• indigestion
• unpleasant breath and body odor
• heartburn
• fatigue

Uncommon side effects:

• leg pain
• scoliosis (curvature of the spine)
• bone fragility
• hair color changes
• seizures
• nervousness
• hallucinations
• kidney effects manifested by swelling of the limbs and weight gain

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of PROCYSBI

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the bottle after EXP. The expiry date is the last day of the month indicated.

Do not take this medicine if the aluminum seal has been open for more than 30 days. Discard the opened bottle and use a new one.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. After opening, do not store above 25 °C. Keep the container perfectly closed to protect it from light and moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and additional information

Composition of PROCYSBI

• The active substance is cysteamine (in the form of mercaptamine bitartrate).

PROCYSBI 25 mg hard gastro-resistant capsules

Each hard gastro-resistant capsule contains 25 mg of cysteamine.

PROCYSBI 75 mg hard gastro-resistant capsules

Each hard gastro-resistant capsule contains 75 mg of cysteamine.

• The other ingredients are:

• Of the capsules: microcrystalline cellulose, methacrylic acid-ethyl acrylate copolymer (1:1), hypromellose, talc, triethyl citrate, and sodium lauryl sulfate (see section "PROCYSBI contains sodium").
• Of the capsule shell: gelatin, titanium dioxide (E171), and indigo carmine (E132).
• Of the printing ink: shellac gum, povidone (K-17), and titanium dioxide (E171).

Appearance and package contents of the product

• PROCYSBI 25 mg is presented in the form of hard gastro-resistant capsules (size 15.9 x 5.8 mm). The light blue cap has the logo "PRO" printed in white ink and the light blue body of the capsule has "25 mg" printed in white ink. A white plastic bottle contains 60 capsules. The cap is child-resistant and has an aluminum seal. Each bottle contains two plastic cylinders used to provide additional protection against moisture and air.

• PROCYSBI 75 mg is presented in the form of hard gastro-resistant capsules (size 21.7 x 7.6 mm). The dark blue cap has the logo "PRO" printed in white ink and the light blue body of the capsule has "75 mg" printed in white ink. A white plastic bottle contains 250 capsules. The cap is child-resistant and has an aluminum seal. Each bottle contains three plastic cylinders used to provide additional protection against moisture and air.

• Keep the cylinders inside each bottle during use. The cylinders can be discarded with the bottle after use.

Marketing authorization holder

Chiesi Farmaceutici S.p.A.

Via Palermo 26/A

43122 Parma

Italy

Manufacturer

Chiesi Farmaceutici S.p.A.

Via San Leonardo 96

43122 Parma

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website http://www.ema.europa.eu.