SAPROPTERIN DIPHARMA 100 mg SOLUBLE TABLETS

Introduction

Package Leaflet: Information for the User

Sapropterina Dipharma 100 mg Soluble Tablets

dihydrochloride of sapropterina (sapropterin dihydrochloride)

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 pack

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

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

Sapropterina Dipharma 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 Dipharma 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 Dipharma reduces these levels in some patients who respond to BH4 and may 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 levels of this amino acid increase, having harmful effects. By replacing the BH4 that the body cannot produce, Sapropterina Dipharma 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 Dipharma

Do not take Sapropterina Dipharma

• 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 Dipharma, especially:

• if you are 65 years 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 Dipharma, your doctor will perform blood tests to check the content of phenylalanine and tyrosine and decide whether to adjust the dose of Sapropterina Dipharma or the diet if necessary.

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

Using Sapropterina Dipharma 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)
• antibiotics (e.g., trimethoprim)
• medicines that cause blood vessels to dilate (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 are planning to have a baby, ask your doctor or pharmacist for advice before taking 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 may be harmful to you and your baby. Your doctor will monitor the restriction of phenylalanine intake with 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 Dipharma is not expected to affect your ability to drive or use machines.

Sapropterina Dipharma contains sodium

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

3. How to take Sapropterina Dipharma

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 Dipharma in patients with PKU is 10 mg per kg of body weight. Take Sapropterina Dipharma 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 Dipharma in patients with BH4 deficiency is 2 to 5 mg per kg of body weight. Take Sapropterina Dipharma 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 faster, 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 Dipharma preparation with a meal within 15 to 20 minutes after preparation.

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 Sapropterina Dipharma tablets needed for a dose
• the amount of water needed to mix a dose of Sapropterin Dipharma
• the amount of solution to give to the child for the prescribed dose.

The child should drink the Sapropterina Dipharma solution with a meal.

Give the child the prescribed amount of solution within 15 to 20 minutes after dissolving the tablets.

If you cannot give the child the dose within 15 to 20 minutes after 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 Dipharma to the child

• The number of Sapropterina Dipharma 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 to stir
• 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., if your doctor told you to use 20 ml to dissolve one Sapropterin Dipharma tablet). Check that the amount of liquid aligns (at the graduation mark corresponding in 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 Dipharma 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 administration 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, releasing a small amount at a time, until you have administered all the solution contained in the oral syringe.
• 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 Dipharma than you should

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

If you forget to take Sapropterin Dipharma

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

If you stop taking Sapropterin Dipharma

Do not stop taking Sapropterina Dipharma without talking to your doctor first, because phenylalanine levels in the blood 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, red, 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 having 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 via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Sapropterina Dipharma

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 and blister after EXP. The expiry date is the last day of the month stated.

This medicine does not require any special storage temperature.

Keep the bottle tightly closed to protect it from moisture.

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

6. Contents of the pack and other information

Composition of Sapropterina Dipharma

• 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 type A, copovidone K 28, ascorbic acid (E300), sodium stearyl fumarate, riboflavin (E101), and colloidal anhydrous silica (E551). See section 2: "Sapropterina Dipharma contains sodium".

Appearance of the product and pack contents

Sapropterina Dipharma 100 mg soluble tablets are round, white to off-white tablets, approximately 10 mm x 3.65 mm, marked with "11" on one side and a score line on the other side.

The score line should not be used to divide the tablet.

They are available in a child-resistant closure bottle with a desiccant (silica). Each bottle contains 30 or 120 soluble tablets.

Not all pack sizes may be marketed.

Marketing authorisation holder

Dipharma Arzneimittel GmbH

Offheimer Weg 33

65549 Limburg a. d. Lahn

Germany

Manufacturer

Depo-Pack S.r.l.

Via Giovanni Morandi 28

21047 Saronno (VA)

Italy

or

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

Date of last revision of this leaflet:

Other sources of information

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.