SAPROPTERIN STADA 100 mg ORALLY DISINTEGRATING TABLETS

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 you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Sapropterina Stada and what is it used for
2. What you need to know before you take Sapropterina Stada
3. How to take Sapropterina Stada
4. Possible side effects

5 Storage of Sapropterina Stada

1. Contents of the pack and further information

1. What is Sapropterina Stada and what is it used for

Sapropterina Stada contains the active substance sapropterina, which is a synthetic copy of a substance naturally found in the body called tetrahydrobiopterin (BH4). BH4 is necessary in the body to convert an amino acid called phenylalanine into another amino acid called tyrosine.

Sapropterina is used to treat hyperphenylalaninemia (HPA) or phenylketonuria (PKU) in patients of any age. HPA and PKU are due to abnormally high levels of phenylalanine in the blood that can be harmful. Sapropterina reduces these levels in some patients who respond to BH4 and can help increase the amount of phenylalanine that can be included in the diet.

This medicine is also used to treat a hereditary disease called BH4 deficiency in patients of any age, in which the body cannot produce enough BH4.

Because BH4 levels are very low, the body cannot properly use phenylalanine and the levels of this amino acid increase, having harmful effects. By replacing the BH4 that the body cannot produce, sapropterina reduces the harmful excess of phenylalanine in the blood and increases tolerance to dietary phenylalanine.

2. What you need to know before you take Sapropterina Stada

Do not take Sapropterina Stada

If you are allergic to sapropterina or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take sapropterina, especially:

• if you are 65 years of age or older
• if you have kidney or liver problems
• if you are ill. It is recommended to consult with your doctor in case of illness since blood phenylalanine levels may increase
• if you have a predisposition to seizures

When you are treated with sapropterina, your doctor will perform blood tests to check the content of phenylalanine and tyrosine and decide whether to adjust the dose of sapropterina or the diet if necessary.

You must continue the dietary treatment as recommended by your doctor. Do not change your diet without telling your doctor. Even if you take sapropterina, if your blood phenylalanine levels are not well controlled, you may have serious neurological problems. Your doctor must continue to monitor your blood phenylalanine levels frequently during treatment with sapropterina, to ensure they are not too high or too low.

Using Sapropterina Stada with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. In particular, you should tell your doctor if you are using:

• levodopa (to treat Parkinson's disease)
• cancer treatments (e.g., methotrexate)
• antibacterial infection treatments (e.g., trimethoprim)
• medicines that cause blood vessel dilation (e.g., glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), sodium nitroprusside (SNP), molsidomine, minoxidil).

Pregnancy and breastfeeding

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.

If you are pregnant, your doctor will tell you how to properly control phenylalanine levels. If they are not strictly controlled before pregnancy or when you become pregnant, it can be harmful to you and your baby. Your doctor will monitor the restriction of phenylalanine intake with the diet before and during pregnancy.

If a strict diet does not satisfactorily reduce the amount of phenylalanine in the blood, your doctor will consider whether you should take this medicine.

You should not use this medicine during breastfeeding.

Driving and using machines

Sapropterina is not expected to affect your ability to drive and use machines.

Important information about some of the ingredients of Sapropterina Stada

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

3. How to take Sapropterina Stada

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

Dose for PKU

The recommended initial dose of sapropterina in patients with PKU is 10 mg per kg of body weight. Take sapropterina once a day, with a meal to increase absorption, and at the same time each day, preferably in the morning. Your doctor may adjust the dose, usually between 5 and 20 mg daily per kg of body weight, according to your condition.

Dose for BH4 deficiency

The recommended initial dose of sapropterina in patients with BH4 deficiency is 2 to 5 mg per kg of body weight. Take sapropterina with a meal to increase absorption. Divide the total daily dose into 2 or 3 doses administered throughout the day. Your doctor may adjust the dose up to 20 mg daily per kg of body weight, according to your condition.

The following table is an example of how to calculate the appropriate dose

Method of administration

For patients with PKU, the total daily dose is taken once a day and at the same time each day, preferably in the morning.

For patients with BH4 deficiency, the total daily dose is divided into 2 or 3 doses distributed throughout the day.

Use in all patients

Place the prescribed tablets in a glass or cup of water, as described exactly below, and stir until they dissolve.

The tablets may take a few minutes to dissolve. To help the tablets dissolve, you can crush them. You may see small particles in the solution that will not affect the effectiveness of the medicine. Drink the dissolved sapropterina preparation with a meal within 15 to 20 minutes of preparation.

Do not ingest the desiccant included in the bottle.

Use in patients with a body weight over 20 kg

Place the tablets in a glass or cup (120 to 240 ml) of water and stir until they dissolve.

Use in children up to 20 kg of body weight

The dose is based on body weight, which will change as the child grows. Your doctor will tell you:

• the number of sapropterina tablets needed for a dose
• the amount of water needed to mix a dose of sapropterina
• the amount of solution to administer to the child for the prescribed dose The child should drink the sapropterina solution with a meal.

Administer the prescribed amount of solution to the child within 15 to 20 minutes of dissolution. If you cannot administer the dose to the child within 15 to 20 minutes of dissolution, you will need to prepare a new solution, as the unused solution should not be used after 20 minutes.

Materials needed to prepare and administer the dose of sapropterina to the child

• The number of sapropterina tablets needed for a dose
• A medicine cup with graduation marks corresponding to 20, 40, 60, and 80 ml
• A glass or cup
• A spoon or clean utensil for stirring
• An oral syringe (graduated in 1 ml divisions) (a 10 ml syringe for administration of volumes ≤10 ml or a 20 ml syringe for administration of volumes >10 ml)

Ask your doctor for the medicine cup and the 10 ml or 20 ml oral syringe if you do not have these materials.

Steps for preparation and administration of the dose:

• Place the prescribed tablets in the medicine cup. Pour into the medicine cup the amount of water indicated by your doctor (e.g., your doctor told you to use 20 ml to dissolve one sapropterina tablet). Check that the amount of liquid aligns (at the graduation mark on the medicine cup) with the amount indicated by your doctor. Stir with the spoon or clean utensil until the tablets dissolve.
• If your doctor told you to administer only part of the solution, insert the tip of the oral syringe into the medicine cup. Slowly pull the plunger back to draw up the amount indicated by your doctor.
• Then transfer the solution to a glass or dosing cup by slowly pushing the plunger until all the solution previously drawn into the oral syringe is inside (e.g., if your doctor told you to dissolve two sapropterina tablets in 40 ml of water and administer 30 ml to the child, you will need to use the 20 ml oral syringe twice to draw up the 30 ml (e.g., 20 ml + 10 ml) of solution and transfer it to a glass or dosing cup). Use a 10 ml oral syringe for administration of volumes ≤10 ml or a 20 ml oral syringe for administration of volumes >10 ml.
• If the baby is too small to drink from a glass or cup, you can administer the solution using the oral syringe. Draw up the prescribed volume of prepared solution into the dosing cup and insert the tip of the oral syringe into the baby's mouth. Aim the tip of the oral syringe towards one of the cheeks. Slowly push the plunger, so that a small amount is released at a time, until all the solution contained in the oral syringe is administered.
• Discard any remaining solution. Pull the plunger out of the oral syringe body. Wash both parts of the oral syringe and the dosing cup with warm water and let them air dry. When the oral syringe is dry, put the plunger back into the oral syringe body. Store the oral syringe and medicine cup for the next use.

If you take more Sapropterina Stada than you should

If you take more sapropterina than prescribed, you may experience side effects that can include headache and dizziness. If you take more sapropterina than prescribed, inform your doctor or pharmacist immediately.

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

If you forget to take Sapropterina Stada

Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time.

If you stop taking Sapropterina Stada

Do not stop treatment with sapropterina without discussing it with your doctor first, because phenylalanine levels in the blood may increase.

If you have any further 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.

There have been a few reports of allergic reactions (such as skin rash and severe reactions). The frequency is not known (the frequency cannot be estimated from the available data).

If you have inflamed, reddened, and very itchy areas (hives), runny nose, rapid or irregular heartbeat, swelling of the tongue or throat, sneezing, wheezing, severe breathing difficulties, or dizziness, you may be experiencing a severe allergic reaction to the medicine. If you experience these symptoms, consult your doctor immediately.

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

Headache and runny nose.

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

Sore throat, nasal congestion or stuffiness, cough, diarrhea, vomiting, stomach pain, low phenylalanine levels in blood tests, indigestion, and general discomfort (nausea) (see section 2: "Warnings and precautions").

Unknown frequency (cannot be estimated from the available data)

Gastritis (inflammation of the stomach lining), esophagitis (inflammation of the esophagus lining).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Sapropterina Stada

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

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

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Place the empty packaging and any unused medicine in the pharmacy's SIGRE collection point. If you have any doubts, ask your pharmacist how to dispose of the packaging and unused medicine. This will help protect the environment.

6. Contents of the pack and further information

• The active substance is sapropterina dihydrochloride. Each tablet contains 100 mg of sapropterina dihydrochloride (equivalent to 77 mg of sapropterina).
• The other ingredients are mannitol (E421), crospovidone, calcium hydrogen phosphate, ascorbic acid (E300), riboflavin (E101), and sodium stearyl fumarate.

Appearance of the product and pack contents

Sapropterina Stada 100 mg soluble tablets EFG are white to light yellow, round tablets, 10 mm in size, with "C" marked on one side.

Sapropterina Stada 100 mg soluble tablets EFG are available in:

• HDPE bottles with a desiccant and a polyester coil, closed with a PP cap.

Package sizes: 30 and 120 tablets

• Al/PVC/Al/OPA blisters

Package sizes: 30 and 120 tablets

• Al/PVC/Al/OPA single-dose blisters

Package sizes: 30x1 and 120x1 single-dose tablets

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Manufacturer

STADA Arzneimittel AG,

Stadastrasse 2 - 18,

61118 Bad Vilbel,

Germany

or

Coripharma ehf.,

Reykjavikurvegur 78,

IS -220 Hafnarfjordur,

Iceland

or

Centrafarm Services B.V,

Van de Reijtstraat 31 E,

4814NE Breda,

Netherlands

This medicine is authorised in the Member States of the European Economic Area under the following names:

Denmark

Germany

Iceland

Netherlands

Norway

Spain

Sweden

Date of last revision of this leaflet:December 2023

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