Sapropterin Dipharma 100 mg powder for oral solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Sapropterin Dipharma 100 mg powder for oral solution

Sapropterin Dipharma 500 mg powder for oral solution

sapropterin dihydrochloride

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the 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 Sapropterin Dipharma is and what it is used for

Sapropterin Dipharma contains the active substance sapropterin, which is a synthetic copy of a naturally occurring substance in the body called tetrahydrobiopterin (BH4). BH4 is required in the body to convert an amino acid called phenylalanine into another amino acid called tyrosine.

Sapropterin Dipharma is used to treat hyperphenylalaninaemia (HPA) or phenylketonuria (PKU) in patients of any age. HPA and PKU are caused by abnormally high levels of phenylalanine in the blood, which can be harmful. Sapropterin 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 disorder 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 utilize phenylalanine, leading to increased levels of this amino acid and harmful effects. By replacing the BH4 that the body cannot produce, Sapropterin Dipharma reduces the harmful excess of phenylalanine in the blood and increases tolerance to dietary phenylalanine.

2. What you need to know before starting to take 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 starting to take Sapropterin Dipharma, especially:

• if you are 65 years of age or older
• if you have kidney or liver problems
• if you are unwell. It is recommended to consult your doctor during illness, as blood phenylalanine levels may increase
• if you have a predisposition to seizures

While receiving treatment with Sapropterin Dipharma, your doctor will perform blood tests to monitor your levels of phenylalanine and tyrosine and will decide whether to adjust the dose of Sapropterin Dipharma or your diet, if necessary.

You must continue your dietary treatment as recommended by your doctor. Do not change your diet without informing your doctor. Even when taking Sapropterin Dipharma, if your blood phenylalanine levels are not well controlled, you may experience serious neurological problems. Your doctor must continue to monitor your blood phenylalanine levels regularly during treatment with Sapropterin Dipharma, to ensure they are neither too high nor too low.

Use of Sapropterin Dipharma with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. In particular, you must inform your doctor if you are using:

• levodopa (used to treat Parkinson's disease)
• medicines for the treatment of cancer (e.g., methotrexate)
• medicines for the treatment of bacterial infections (e.g., trimethoprim)
• medicines that cause dilation of blood vessels (e.g., glyceryl trinitrate [GTN], isosorbide dinitrate [ISDN], sodium nitroprusside [SNP], molsidomine, minoxidil).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or are planning 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 manage your phenylalanine levels. If these levels are not strictly controlled before or during pregnancy, it 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 sufficiently reduce the amount of phenylalanine in the blood, your doctor will consider whether you should take this medicine.

You must not use this medicine during breastfeeding.

Driving and use of machines

Sapropterin Dipharma is not expected to affect your ability to drive or operate 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 account in patients with renal impairment or in those on potassium-restricted diets.

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 account in patients with renal impairment or in those on potassium-restricted diets.

3. How to take Sapropterin Dipharma

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor again.

Sapropterin Dipharma 500 mg should 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 a meal to enhance absorption, at the same time each day, preferably in the morning. Your doctor may adjust the dose, usually between 5 and 20 mg per kg per day, depending on your condition.

Dosage for BH4 deficiency

The recommended starting dose of Sapropterin Dipharma in patients with BH4 deficiency is 2 to 5 mg per kg of body weight. Take Sapropterin Dipharma with a meal to enhance absorption. Divide the total daily dose into 2 or 3 doses taken throughout the day. Your doctor may adjust the dose up to 20 mg per kg per day, depending on your condition.

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

Administration method

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

For patients with BH4 deficiency, the total daily dose should be divided into 2 or 3 doses taken throughout the day.

Use in patients with body weight above 20 kg

Make sure you know the dose of Sapropterin Dipharma powder for oral solution 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 how to use Sapropterin Dipharma 100 mg or 500 mg powder for oral solution, or both medications, to prepare the dose.

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

Preparation of the sachet(s)

• Open the sachet(s) of Sapropterin Dipharma powder for oral solution by folding and tearing it(them), or by cutting along the dotted line at the top corner of the sachet.
• Empty the contents of the sachet(s) into 120 to 240 ml of water. After dissolving the powder in water, the resulting solution should be clear, ranging from colourless to yellowish.

Taking the medicine

• Drink the solution within 30 minutes.

Use in children with body weight up to 20 kg

Use only the 100 mg sachets when preparing Sapropterin Dipharma for children with a body weight up to 20 kg.

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

• the number of Sapropterin Dipharma 100 mg sachets required for one dose
• the amount of water needed to mix one dose of Sapropterin Dipharma
• the volume of solution to administer to the child for the prescribed dose.

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

Administer the prescribed volume of solution to the child within 3 minutes after dissolving. If you are unable to administer the dose to the child within 30 minutes after dissolving the powder, a new solution must be prepared, as the unused solution should not be used after 30 minutes.

Materials required to prepare and administer the dose of Sapropterin Dipharma to the child

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

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

Steps for preparing and administering the dose:

• Place the prescribed Sapropterin Dipharma 100 mg sachets into the dosing cup. Pour into the dosing cup the amount of water indicated by your doctor (e.g., if your doctor instructed you to use 20 ml to dissolve one Sapropterin Dipharma tablet). Check that the liquid level aligns (with the corresponding graduation mark on the dosing cup) with the amount indicated by your doctor. Stir with a clean spoon or utensil until the powder dissolves. After dissolving the powder in water, the resulting solution should be clear, ranging from colourless to yellowish.
• If your doctor instructed you to administer only part of the solution, insert the tip of the oral dosing syringe into the dosing cup. Slowly pull back the plunger to withdraw the volume prescribed 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 dosing syringe is transferred (e.g., if your doctor instructed you to dissolve two Sapropterin Dipharma 100 mg sachets in 40 ml of water and administer 30 ml to the child, you will need to use the 20 ml oral dosing syringe twice to withdraw 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 administering volumes ≤ 10 ml or a 20 ml oral syringe for administering volumes > 10 ml.
• If the baby is too young to drink from a glass or cup, you may administer the solution using the oral dosing syringe. Withdraw the prescribed volume of prepared solution from the dosing cup and insert the tip of the oral dosing syringe into the baby's mouth. Aim the tip of the oral dosing syringe towards one of the cheeks. Slowly push the plunger so that a small amount is released at a time, until the entire solution in 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 dosing cup with lukewarm 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 dosing cup for next use.

If you take more Sapropterin Dipharma than you should

If you take more Sapropterin Dipharma than prescribed, you may experience adverse effects, which may include headache and dizziness. If you take more Sapropterin Dipharma than prescribed, inform your doctor or pharmacist immediately.

If you forget to take Sapropterin Dipharma

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

If you stop taking Sapropterin Dipharma

Do not stop treatment with Sapropterin Dipharma without first discussing it with your doctor, as blood phenylalanine levels may increase.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

A few cases of allergic reactions (such as skin rashes and serious reactions) have been reported. Their frequency is unknown (the frequency cannot be estimated from the available data).

If you experience swollen, red and intensely itchy skin areas (urticaria), runny nose, rapid or irregular pulse, swelling of the tongue or throat, sneezing, wheezing, severe breathing difficulty, or dizziness, you may be experiencing a serious allergic reaction to this medicine. If you develop any of these symptoms, consult your doctor immediately.

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

Headache and runny nose.

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

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

Adverse effects with unknown frequency (cannot be estimated from the available data):

Gastritis (inflammation of the stomach lining), oesophagitis (inflammation of the oesophageal lining).

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sapropterin 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 foil and on the packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and other information

Composition of Sapropterin Dipharma

• The active substance is sapropterin dihydrochloride.

Sapropterin Dipharma 100 mg: Each sachet contains 100 mg of sapropterin dihydrochloride (equivalent to 77 mg of sapropterin).

Sapropterin 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. "Sapropterin Dipharma contains potassium".

Appearance of the product and contents of the pack

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.

Packs of 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, PLA 3000

Malta

Date of the most recent revision of this leaflet:

Other sources of information

Detailed information on this medicinal product 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 medicinal products.