SAPROPTERIN AUROVITAS 100 mg SOLUBLE TABLETS

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

Do not take Sapropterina Aurovitas

• if you are allergic to sapropterin 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 this medicine, 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, as blood phenylalanine levels may increase.
• if you have a predisposition to seizures.

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

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

Other medicines and Sapropterina Aurovitas

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 (used to treat Parkinson's disease).
• cancer treatments (e.g., methotrexate).
• antibacterial infection treatments (e.g., trimethoprim).
• medicines that cause blood vessel dilation (such as 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 advise you on how to properly control phenylalanine levels. If they are not strictly controlled before pregnancy or when you become pregnant, it may be harmful to you and your baby. Your doctor will monitor dietary phenylalanine restriction 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

Sapropterin is not expected to affect your ability to drive or use machines.

Sapropterina Aurovitas contains sodium

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

3. How to take Sapropterina Aurovitas

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are in doubt, consult your doctor again.

Dose for PKU

The recommended initial dose of sapropterin 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 sapropterin in patients with BH4 deficiency is 2 to 5 mg per kg of body weight. Take sapropterin 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 sapropterin 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 body weight

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

• the number of sapropterin tablets needed for a dose.
• the amount of water needed to mix a dose of sapropterin.
• the amount of solution to administer to the child for the prescribed dose.

The child should drink the sapropterin solution with a meal.

If you cannot administer the dose to the child within 15 to 20 minutes of dissolving the tablets, 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 sapropterin to the child:

• The number of sapropterin tablets needed for a dose.
• A medicine cup with graduated markings 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 sapropterin tablet). Check that the amount of liquid aligns (at the graduated marking 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 sapropterin 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. Remove the plunger from the body of the oral syringe. 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 body of the syringe. Store the oral syringe and medicine cup for the next use.

If you take more Sapropterina Aurovitas than you should

If you take more sapropterin than prescribed, you may experience side effects that can include headache and dizziness. If you take more sapropterin 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, telephone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Sapropterina Aurovitas

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 Aurovitas

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

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.

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 blood phenylalanine levels, indigestion, and general discomfort (nausea) (see section 2: "Warnings and precautions").

Unknown frequency side effects (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 or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Sapropterina Aurovitas

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 carton, label of the bottle, and blister after EXP. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at the 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 Sapropterina Aurovitas

• The active substance is sapropterin dihydrochloride. Each soluble tablet contains 100 mg of sapropterin dihydrochloride.
• The other ingredients are: mannitol, calcium hydrogen phosphate, crospovidone, ascorbic acid, riboflavin, stearic acid fumarate, and sodium.

Appearance of the product and pack contents

Sapropterina Aurovitas 100 mg Soluble Tablets EFG are soluble, uncoated tablets, white to light yellow in color, round, with the marking "S 1" on one face and smooth on the other. The tablet may be speckled.

Sapropterina Aurovitas 100 mg Soluble Tablets EFG are available in blister packs and HDPE bottles.

Each HDPE bottle contains silica gel as a desiccant.

Pack sizes:

Blister:30 and 120 soluble tablets.

HDPE bottle:30, 120, and 240 soluble tablets.

Single-dose perforated blister:120 × 1 soluble tablets.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Aurovitas Spain, S.A.U.

Avenida de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, 19

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

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

Germany: Sapropterin PUREN 100 mg Tabletten zur Herstellung einer Lösung zum Einnehmen

Spain: Sapropterina Aurovitas 100 mg comprimidos solubles EFG

France: SAPROPTERINE ARROW 100 mg, comprimé pour solution buvable

Italy: Sapropterina Aurobindo

Netherlands: Sapropterine Aurobindo 100 mg, oplosbare tabletten

Portugal: Sapropterina Generis

Sweden: Sapropterin Aurobindo

Date of last revision of this leaflet:January 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/).