Sapropterin Dipharma

Package leaflet: Information for the user

Sapropterin Dipharma 100 mg dispersible tablets

sapropterin dihydrochloride (sapropterini dihydrochloridum)
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Sapropterin Dipharma is and what it is used for
2. What you need to know before taking Sapropterin Dipharma
3. How to take Sapropterin Dipharma
4. Possible side effects
5. How to store Sapropterin 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 sapropterin, which is a synthetic copy of a substance naturally present in our body called tetrahydrobiopterin (BH4). The function of the BH4 molecule is to help the body use an amino acid called phenylalanine to produce another amino acid called tyrosine.

Sapropterina Dipharma is used to treat hyperphenylalaninaemia (HPA) or phenylketonuria (PKU) in patients of any age. HPA and PKU are caused by excessively high levels of phenylalanine in the blood, which 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 an inherited disease called BH4 deficiency, in patients of any age, in which the body cannot produce enough BH4. Due to very low levels of BH4, phenylalanine is not properly metabolized and its levels rise, causing harmful effects. By replacing the BH4 that the body does not produce, Sapropterina Dipharma reduces the harmful effects of excess phenylalanine in the blood and increases tolerance to phenylalanine in the diet.

2. What you need to know before taking Sapropterin Dipharma

Do not take Sapropterin Dipharma

• if you are allergic to sapropterin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking Sapropterin Dipharma, especially:

• if you are over 65 years old
• if you have kidney or liver problems
• if you are unwell. In case of illness, medical advice is recommended, as phenylalanine levels may increase
• if you have a predisposition to seizures

During treatment with Sapropterin Dipharma, your doctor will carry out blood tests to monitor the levels of phenylalanine and tyrosine in your blood and may decide, if necessary, to adjust the dosage of Sapropterin Dipharma or your diet.
You must continue your dietary treatment as recommended by your doctor. Do not change your diet without contacting your doctor. Even if you are taking Sapropterin Dipharma, serious neurological problems may occur if blood phenylalanine levels are not kept under control. During treatment with Sapropterin Dipharma, your doctor must continue to monitor blood phenylalanine levels frequently, to ensure they are not too high or too low.
Other medicines and Sapropterin Dipharma
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. In particular, you must inform your doctor if you are using:

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

Pregnancy, breastfeeding and fertility
If you are pregnant, think you might be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you are pregnant, your doctor will advise you on how to properly control your phenylalanine levels. If phenylalanine levels are not well controlled before or during pregnancy, this may be harmful to you and your baby. Your doctor will monitor the restriction of dietary phenylalanine intake before and during pregnancy.
If a strict diet does not adequately reduce blood phenylalanine levels, your doctor will decide whether you should take this medicine.
You must not take this medicine during breastfeeding.
Driving and using machines
Sapropterin Dipharma is not expected to affect your ability to drive or use machinery.
Sapropterin Dipharma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

3. How to take Sapropterin Dipharma

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Dosage for PKU
The recommended starting dose of Sapropterin Dipharma in patients with PKU is 10 mg per kg of body weight. Take Sapropterin Dipharma once daily with a meal to enhance absorption, always at the same time, preferably in the morning. Your doctor may adjust your dose, usually between 5 and 20 mg per kg of body weight per day, depending on your individual needs.
Dosage for BH4 deficiency
The recommended starting dose of Sapropterin Dipharma in patients with BH4 deficiency ranges from 2 to 5 mg per kg of body weight. Take Sapropterin Dipharma with meals to enhance absorption. Divide the total daily dose into 2 or 3 administrations taken throughout the day. Your doctor may adjust your dose up to 20 mg per kg of body weight per day, depending on your individual needs.
The table below is an example of how an appropriate dose is calculated

Administration method
For patients with PKU, the total daily dose should be taken once daily, always at the same time, preferably in the morning.
For patients with BH4 deficiency, the total daily dose should be divided into 2 or 3 administrations throughout the day.

Use in all patients
Transfer the prescribed number of tablets into a glass or cup of water or apple juice, as described in detail below, and stir until dissolved.
The tablets may take several minutes to dissolve. To speed up dissolution, the tablets may be crushed. Small particles may be visible in the solution, but they will not affect the effectiveness of the medicine.
Drink the dissolved Sapropterin Dipharma preparation with a meal, within 15 to 20 minutes after preparation.
Sapropterin Dipharma soluble tablets may also be crushed and mixed with a small amount of soft food such as apple puree or pudding.
If necessary, Sapropterin Dipharma soluble tablets may be administered via an enteral feeding tube. For detailed information, please consult your doctor, pharmacist, or nurse.

Use in patients with body weight above 20 kg
Place the tablets in a glass or cup (60 – 240 ml) of water or apple juice and stir until dissolved. The soluble tablets may also be mixed with a small amount of soft food.

Use in children with body weight up to 20 kg
The dose depends on body weight, which changes as your child grows. Your doctor will inform you:

• the number of Sapropterin Dipharma tablets required for one dose
• the amount of water or apple juice needed to prepare one dose of Sapropterin Dipharma
• the amount of solution to administer to your child for the prescribed dose.

Your child must drink the solution with a meal.
Give your child the prescribed amount of solution within 15 or 20 minutes after dissolution. If you cannot administer the dose to your child within 15 or 20 minutes after the tablets have dissolved, you must prepare a fresh solution, as the unused solution must not be used after 20 minutes have passed. For doses equal to 100 mg or multiples of 100 mg, the soluble tablets may be mixed with a small amount of soft food such as apple puree or pudding.

Materials needed to prepare and administer the dose of Sapropterin Dipharma to your child

• The number of Sapropterin Dipharma tablets required for one dose
• A graduated glass with markings at 20, 40, 60, and 80 ml
• A glass or cup
• A teaspoon or clean utensil for stirring
• An oral dosing syringe (with 1 ml graduations) (10 ml syringe for administering volumes ≤ 10 ml or 20 ml syringe for administering volumes > 10 ml)

If you do not have the graduated glass for dissolving the tablets or the 10 ml or 20 ml syringe, please request them from your doctor.

Steps for preparing and administering the dose:

• Transfer the prescribed number of tablets into the graduated glass. Add the amount of water or apple juice indicated by your doctor (for example, your doctor has instructed you to use 20 ml to dissolve one Sapropterin Dipharma tablet). Ensure that the volume of liquid corresponds exactly to the amount prescribed by your doctor. Stir with a teaspoon or clean utensil until the tablets are completely dissolved.
• If your doctor has instructed you to administer only part of the solution, immerse the tip of the oral dosing syringe into the dosing glass. Slowly pull back the plunger to draw up the amount prescribed by your doctor.
• Transfer the solution by slowly pushing the plunger to empty the entire contents of the oral dosing syringe into a glass or cup for administration (for example, if your doctor instructed you to dissolve two Sapropterin Dipharma tablets in 40 ml of water or apple juice and to give 30 ml to your child, you must use the 20 ml oral dosing syringe twice to draw up 30 ml (e.g., 20 ml + 10 ml) of solution and transfer it into a glass or cup for administration). Use a 10 ml oral dosing syringe for administering volumes ≤ 10 ml and a 20 ml oral dosing syringe for administering volumes > 10 ml.
• If your child is too young to drink from a glass or cup, you may administer the solution using the oral dosing syringe. Draw up the prescribed volume from the solution prepared in the graduated glass and place the tip of the oral dosing syringe into your child’s mouth. Direct the tip of the syringe toward the cheek. Slowly push the plunger to administer the solution gradually, until the entire content of the oral dosing syringe has been administered.
• Discard any remaining solution. Remove the plunger from the barrel of the oral dosing syringe. Wash both parts of the oral dosing syringe and the graduated glass with warm water, and allow them to air dry. Once the oral dosing syringe is dry, reinsert the plunger into the barrel. Store the oral dosing syringe and the graduated glass for future use.

If you take more Sapropterin Dipharma than you should
Taking more Sapropterin Dipharma than prescribed may cause adverse effects, including headache and dizziness. If you take more than the prescribed dose, contact your doctor or pharmacist immediately.

If you forget to take Sapropterin Dipharma
Do not take a double dose to make up for the missed dose. Take the next dose at your usual scheduled time.

If you stop taking Sapropterin Dipharma
Do not stop taking Sapropterin Dipharma without first consulting your doctor, as this may lead to an increase in blood phenylalanine levels.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
A few cases of allergic reactions (such as skin rashes and severe reactions) have been reported. Their frequency is unknown (the frequency cannot be estimated from the available data).
If you experience red, itchy, raised areas on the skin (urticaria), runny nose, rapid or irregular heartbeat, swelling of the tongue and throat, sneezing, wheezing, severe breathing difficulties, or dizziness, this may indicate a serious allergic reaction to the medicine. If you notice these symptoms, contact 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 blocked nose, cough, diarrhoea, vomiting, stomach ache, low levels of phenylalanine in the blood, indigestion, and nausea (see section 2: "Warnings and precautions").

Side effects with unknown frequency (the frequency cannot be estimated from the available data):
Gastritis (inflammation of the inner lining of the stomach), oesophagitis (inflammation of the inner lining of the oesophagus).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sapropterin Dipharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Keep the bottle tightly closed to protect the medicine from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sapropterin Dipharma contains

• The active substance is sapropterin dihydrochloride. Each tablet contains 100 mg of sapropterin dihydrochloride, equivalent to 77 mg of sapropterin.
• The other components are: mannitol (E421), crospovidone type A, copovidone K 28, ascorbic acid (E300), sodium stearyl fumarate, riboflavin (E101), colloidal anhydrous silica (E551). See section 2 “Sapropterin Dipharma contains sodium”.

Description of the appearance of Sapropterin Dipharma and package contents
Sapropterin Dipharma 100 mg dispersible tablets are whitish-yellow in colour, approximately 10 mm x 3.65 mm, with "11" printed on one side and a score line on the other side.
The score line is not intended for breaking the tablet.
The product is available in bottles with child-resistant closure and screw cap, containing desiccant (silica).
Pack sizes of 30 or 120 dispersible 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 PLA3000
Malta

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/ .

Package leaflet: Information for the user

Sapropterin Dipharma 100 mg oral solution powder, 500 mg oral solution powder

sapropterin dihydrochloride (sapropterini dihydrochloridum)
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Sapropterin Dipharma is and what it is used for
2. What you need to know before taking Sapropterin Dipharma
3. How to take Sapropterin Dipharma
4. Possible side effects
5. How to store Sapropterin Dipharma
6. Package contents and other information

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

Sapropterina Dipharma contains the active substance sapropterin, which is a synthetic copy of a substance naturally present in our body called tetrahydrobiopterin (BH4). The function of the BH4 molecule is to help the body use an amino acid called phenylalanine to produce another amino acid called tyrosine.

Sapropterina Dipharma is used to treat hyperphenylalaninaemia (HPA) or phenylketonuria (PKU) in patients of any age. HPA and PKU are caused by excessively high levels of phenylalanine in the blood, which 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 an inherited disease called BH4 deficiency, in patients of any age, in which the body cannot produce enough BH4. Due to very low levels of BH4, phenylalanine is not properly metabolized, leading to its accumulation and harmful effects. By replacing the BH4 that the body cannot produce, Sapropterina Dipharma reduces the harmful effects of excess phenylalanine in the blood and increases tolerance to phenylalanine in the diet.

2. What you need to know before taking Sapropterin Dipharma

Do not take Sapropterin Dipharma

• if you are allergic to sapropterin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking Sapropterin Dipharma, especially:

• if you are over 65 years old
• if you have kidney or liver problems
• if you are unwell. In case of illness, medical advice is recommended, as phenylalanine levels may increase
• if you are prone to seizures

During treatment with Sapropterin Dipharma, your doctor will carry out blood tests to monitor the levels of phenylalanine and tyrosine in your blood and may decide, if necessary, to adjust the dose of Sapropterin Dipharma or your diet.
You must continue your dietary treatment as recommended by your doctor. Do not change your diet without consulting your doctor. Even if you are taking Sapropterin Dipharma, serious neurological problems may occur if phenylalanine levels in the blood are not kept under control. During treatment with Sapropterin Dipharma, your doctor must continue to monitor phenylalanine blood levels frequently, to ensure they are not too high or too low.
Other medicines and Sapropterin Dipharma
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. In particular, you must inform your doctor if you are using:

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

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you are pregnant, your doctor will advise you on how to properly control your phenylalanine levels. If phenylalanine levels are not well controlled before or during pregnancy, this may be harmful to you and your baby. Your doctor will monitor dietary restriction of phenylalanine intake before and during pregnancy.
If a strict diet does not adequately reduce phenylalanine blood levels, your doctor will decide whether you should take this medicine.
You must not take this medicine during breastfeeding.
Driving and using machines
Sapropterin Dipharma is not expected to affect your ability to drive or use machinery.
Sapropterin Dipharma contains potassium
Sapropterin Dipharma 100 mg powder for oral solution
This medicine contains 0.3 mmol (11.7 mg) of potassium per sachet, which should be taken into consideration in patients with impaired renal function or those on a low-potassium diet.
Sapropterin Dipharma 500 mg powder for oral solution
This medicine contains 1.6 mmol (62.6 mg) of potassium per sachet, which should be taken into consideration in patients with impaired renal function or those on a low-potassium diet.

3. How to take Sapropterin Dipharma

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Sapropterin Dipharma 500 mg must only be used in patients with a body weight above 25 kg.

Dosage for PKU
The recommended starting dose of Sapropterin Dipharma in patients with PKU is 10 mg per kg of body weight. Take Sapropterin Dipharma once daily, with meals to enhance its absorption, always at the same time and preferably in the morning. Your doctor may adjust your dose, typically between 5 and 20 mg per day per kg of body weight, depending on your individual needs.

Dosage for BH4 deficiency
The recommended starting dose of Sapropterin Dipharma in patients with BH4 deficiency ranges between 2 and 5 mg per kg of body weight. Take Sapropterin Dipharma with meals to enhance its absorption. Divide the total daily dose into 2 or 3 administrations taken throughout the day. Your doctor may adjust your dose up to 20 mg per day per kg of body weight, depending on your individual needs.

The table below is an example of how an appropriate dose is calculated

Administration method
For patients with PKU, the total daily dose should be taken once daily, always at the same time, preferably in the morning.
For patients with BH4 deficiency, the total daily dose is divided into 2 or 3 administrations throughout the day.

Use in patients with body weight above 20 kg
Make sure you know the dose of Sapropterin Dipharma powder prescribed by your doctor.

Sapropterin Dipharma 100 mg powder for oral solution
For higher doses, your doctor may also prescribe Sapropterin Dipharma 500 mg powder for oral solution.

Sapropterin Dipharma 500 mg powder for oral solution
For the exact dose, your doctor may also prescribe Sapropterin Dipharma 100 mg powder for oral solution.

Ensure you know whether you should use only Sapropterin Dipharma 100 mg or 500 mg powder for oral solution, or both medicines, to prepare your dose.

Open the sachet(s) only when you are ready to use them.

Preparation of the sachet(s)

• Open the sachet(s) of Sapropterin Dipharma powder for oral solution by folding (1) and tearing (2) or cutting along the dotted line in the upper right corner of the sachet.
• Empty (3) the contents of the sachet(s) into 60–240 ml of water or apple juice. After dissolving Sapropterin Dipharma powder in water, the solution should appear clear, colourless to yellow. The powder for oral solution may also be mixed with a small amount of soft food such as apple puree or pudding.

(1) (2) (3)

Taking the medicine

• Drink the solution or consume the mixture within 30 minutes.

If necessary, Sapropterin Dipharma powder for oral solution can be administered via an enteral feeding tube. For detailed instructions on how to proceed, please consult your doctor, pharmacist, or nurse.

Use in children with body weight up to 20 kg
For the preparation of Sapropterin Dipharma in children with body weight up to 20 kg, use only 100 mg sachets.

The dose depends on body weight, which changes as your child grows. Your doctor will inform you:

• the number of Sapropterin Dipharma 100 mg sachets required for one dose
• the amount of water or apple juice needed to prepare one dose of Sapropterin Dipharma
• the amount of solution to administer to your child for the prescribed dose.

Your child must drink the solution together with a meal.
Give your child the prescribed amount of solution within 30 minutes after dissolution. If you are unable to administer the dose to your child within 30 minutes of dissolving the powder, you must prepare a new solution, as the unused solution must not be used after 30 minutes have passed.

For doses equal to 100 mg or multiples of 100 mg, the powder for oral solution may also be mixed with a small amount of soft food such as apple puree or pudding.

Materials needed to prepare and administer the dose of Sapropterin Dipharma to your child

• The number of Sapropterin Dipharma 100 mg sachets required for one dose
• A graduated glass with markings at 20, 40, 60, and 80 ml
• A glass or cup
• A teaspoon or clean utensil for mixing
• An oral dosing syringe (with 1 ml graduations) (10 ml syringe for administering volumes ≤ 10 ml or 20 ml syringe for administering volumes > 10 ml)

If you do not have the graduated glass for dissolving the sachets or the 10 ml or 20 ml oral syringe, please request them from your doctor.

Steps for preparing and administering the dose:

• Transfer the prescribed number of Sapropterin Dipharma 100 mg sachets into the graduated glass. Pour into the graduated glass the amount of water or apple juice indicated by your doctor (for example, your doctor may have instructed you to use 20 ml to dissolve one sachet of Sapropterin Dipharma). Ensure that the amount of liquid corresponds exactly to the amount indicated by your doctor.

Mix with a teaspoon or clean utensil until the contents of the sachet are completely dissolved. After dissolving the powder in water, the solution should appear clear, colourless to yellow.

• If your doctor has instructed you to administer only part of the solution, immerse the tip of the oral dosing syringe into the dosing glass. Slowly pull back the plunger to withdraw the amount prescribed by your doctor.
• Transfer the solution by slowly pressing the plunger until all the solution contained in the oral syringe has been transferred into a glass or cup for administration (for example, if your doctor instructed you to dissolve two Sapropterin Dipharma 100 mg sachets in 40 ml of water or apple juice and to give 30 ml to your child, you must use the 20 ml oral syringe twice to withdraw 30 ml (e.g., 20 ml + 10 ml) of solution and transfer it into a glass or cup for administration). Use a 10 ml oral syringe for administering volumes ≤ 10 ml and a 20 ml oral syringe for administering volumes > 10 ml.
• If your child is too young to drink from a glass or cup, you may administer the solution using the oral dosing syringe. Draw up the prescribed volume from the solution prepared in the graduated glass and place the tip of the oral dosing syringe into your child’s mouth. Direct the tip of the syringe toward the cheek. Slowly press the plunger and administer the solution gradually until the entire content of the syringe has been administered.
• Discard any remaining solution. Remove the plunger from the barrel of the oral dosing syringe. Wash both parts of the oral dosing syringe and the graduated glass with warm water and allow them to air dry. When the oral dosing syringe is dry, reinsert the plunger into the barrel. Store the oral dosing syringe and the graduated glass for future use.

If you take more Sapropterin Dipharma than you should
If you take a dose of Sapropterin Dipharma higher than prescribed, adverse effects such as headache and dizziness may occur. If you take more Sapropterin Dipharma than prescribed, contact your doctor or pharmacist immediately.

If you forget to take Sapropterin Dipharma
Do not take a double dose to make up for the missed dose. Take the next dose at your usual scheduled time.

If you stop taking Sapropterin Dipharma
Do not stop taking Sapropterin Dipharma without first consulting your doctor, as this may lead to an increase in blood phenylalanine levels.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
A few cases of allergic reactions (such as skin rashes and severe reactions) have been reported. Their frequency is unknown (the frequency cannot be determined from the available data).
If you develop red, itchy, raised skin areas (urticaria), runny nose, rapid or irregular heartbeat, swelling of the tongue and throat, sneezing, wheezing, severe breathing difficulties, or dizziness, this may indicate a serious allergic reaction to the medicine. If you experience these symptoms, seek medical advice 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 blocked nose, cough, diarrhoea, vomiting, stomach ache, low levels of phenylalanine in the blood, indigestion, and nausea (see section 2: "Warnings and precautions").

Side effects with unknown frequency (the frequency cannot be determined from the available data):
Gastritis (inflammation of the inner lining of the stomach), oesophagitis (inflammation of the inner lining of the oesophagus).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sapropterin Dipharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the sachet and carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sapropterina Dipharma contains

• The active substance is sapropterin dihydrochloride.
  Sapropterina Dipharma 100 mg: Each sachet contains 100 mg of sapropterin dihydrochloride, equivalent to 77 mg of sapropterin.
  Sapropterina Dipharma 500 mg: Each sachet contains 500 mg of sapropterin dihydrochloride, equivalent to 384 mg of sapropterin.
• The other components are: mannitol (E421), potassium citrate (E332), sucralose (E955), and ascorbic acid (E300). See section 2 “Sapropterina Dipharma contains potassium”.

Description of the appearance of Sapropterina Dipharma and package contents
The oral solution powder is white to slightly yellowish in colour. The powder is contained in single-dose sachets containing 100 mg or 500 mg of sapropterin dihydrochloride.
Pack sizes: 30 sachets.

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 PLA3000
Malta

Further information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.
The latest approved instructions “Preparation of the sachet(s)” for this medicinal product are available by scanning with a smartphone the QR code included on the outer packaging. The same information is also available at the following URL: https://leafletsapropterin.ch/