Prospect: information for the user

Sapropterina Dipharma 100 mg powder for oral solution

Sapropterina Dipharma 500 mg powder for oral solution

dihydrochloride of sapropterin (sapropterin dihydrochloride)

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Sapropterina Dipharma contains the active ingredient sapropterin, which is a synthetic copy of a substance 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 caused by 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 medication 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 use phenylalanine properly and phenylalanine levels increase, having harmful effects. By substituting the BH4 that the body cannot produce, Sapropterina Dipharma reduces the damaging excess of phenylalanine in the blood and increases tolerance to phenylalanine in the diet.

Do not take Sapropterin Dipharma

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Sapropterin 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 receiving treatment with Sapropterin Dipharma, your doctor will perform blood tests to verify the content of phenylalanine and tyrosine and decide to adjust the dose of Sapropterin Dipharma or the diet as necessary.

You must continue the dietary treatment according to your doctor's recommendations. Do not change your diet without informing your doctor. Even though you take Sapropterin Dipharma, if your blood phenylalanine levels are not well controlled, you may experience severe neurological problems. Your doctor must continue to monitor your blood phenylalanine levels frequently during treatment with Sapropterin Dipharma,to ensure they are not too high or too low.

Use of Sapropterin Dipharma with other medications

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

• levodopa (to treat Parkinson's disease)
• medications for cancer treatment (e.g., methotrexate)
• medications for bacterial infection treatment (e.g., trimethoprim)
• medications 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, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

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

You should not use this medication during breastfeeding.

Driving and operating machinery

Sapropterin Dipharma is not expected to affect your ability to drive and operate machinery.

Sapropterin Dipharma contains potassium

Sapropterin Dipharma 100 mg powder for oral solution

This medication contains 0.3 mmol (11.7 mg) of potassium per sachet, which should be taken into account in patients with renal insufficiency or patients with low-potassium diets.

Sapropterin Dipharma 500 mg powder for oral solution

This medication contains 1.6 mmol (62.6 mg) of potassium per sachet, which should be taken into account in patients with renal insufficiency or patients with low-potassium diets.

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

Sapropterin Dipharma 500 mg should only be used in patients with a body weight above 25 kg.

Dose for PKU

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

Dose for BH4 deficiency

The initial recommended 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 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 weight, according to your condition.

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

Administration form

For patients with PKU, the total daily dose is taken once a day and at the same time every 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 patients with a body weight above 20 kg

Make sure you know the dose of Sapropterin Dipharma powder that your doctor has prescribed.

Sapropterin Dipharma 100 mg powder for oral solution

Your doctor may also prescribe Sapropterin Dipharma 500 mg powder for oral solution for higher doses.

Sapropterin Dipharma 500 mg powder for oral solution

Your doctor may also prescribe Sapropterin Dipharma 100 mg powder for oral solution for the exact dose.

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

Only open the packet (or packets) when you are ready to use it (them).

Preparing the packet (or packets)

• Open the packet (or packets) of Sapropterin Dipharma powder for oral solution by folding and tearing it, or by cutting it along the dotted line at the top of the packet.
• Empty the contents of the packet (or packets) into 120 to 240 ml of water. After dissolving the powder in water, the resulting solution should be transparent, colorless, or yellowish.

Intake of the medication

• Drink the solution within 30 minutes.

Use in children up to 20 kg of body weight

Only use the 100 mg packets if you are preparing Sapropterin Dipharma for children with a body weight of up to 20 kg.

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

• the number of 100 mg packets of Sapropterin Dipharma needed for a dose
• the amount of water needed to mix a dose of Sapropterin Dipharma
• the amount of solution to administer to the child for the prescribed dose.

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

Administer the solution to the child within 3 minutes of its dissolution. If you cannot administer the dose to the child within 30 minutes of dissolving the powder, you will have to prepare a new solution, as the unused solution should not be used after 30 minutes.

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

• The number of 100 mg packets of Sapropterin Dipharma needed for a dose
• A medication cup with markings corresponding to 20, 40, 60, and 80 ml
• A cup or a medication cup
• A spoon or a clean utensil to stir
• An oral syringe (graduated in 1 ml divisions) (a 10 ml syringe for administering volumes ≤ 10 ml or a 20 ml syringe for administering volumes > 10 ml)

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

Steps for preparation and administration:

• Place the prescribed packets of Sapropterin Dipharma 100 mg in the medication cup. Pour the indicated amount of water into the dosing cup (e.g., if your doctor told you to use 20 ml to dissolve a Sapropterin Dipharma tablet). Check that the amount of liquid aligns (with the corresponding graduation mark on the medication cup) with the amount indicated by your doctor. Stir with a spoon or a clean utensil until the powder dissolves. After dissolving the powder in water, the resulting solution should be transparent, colorless, or yellowish.
• If your doctor told you to administer only a part of the solution, insert the tip of the oral syringe into the medication cup. Pull the plunger back slowly to extract the indicated amount.
• Next, transfer the solution to a cup or a dosing cup by pushing the plunger slowly until all the solution previously introduced into the oral syringe is inside (e.g., if your doctor told you to dissolve two 100 mg packets of Sapropterin Dipharma in 40 ml of water and administer 30 ml to the child, you will have to use the 20 ml oral syringe twice to extract the 30 ml (e.g., 20 ml + 10 ml) of solution and transfer it to a cup or a medication cup for administration). Use an oral syringe of 10 ml for administering volumes ≤ 10 ml or an oral syringe of 20 ml for administering volumes > 10 ml.
• If the baby is too small to drink from a cup or a medication cup, you can administer the solution using the oral syringe. Extract the prescribed volume of solution prepared in the dosing cup and insert the tip of the oral syringe into the baby's mouth. Point the tip of the oral syringe towards one cheek. Push the plunger slowly, releasing a small amount at a time, until all the solution contained in the oral syringe is administered.
• Discard any remaining solution. Extract 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, reinsert the plunger into the body of the oral syringe. Store the oral syringe and the medication cup for the next use.

If you take more Sapropterin Dipharma than you should

If you take more Sapropterin Dipharma than prescribed, you may experience adverse effects that may include headaches 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 compensate for the missed doses. Take the next dose at the usual time.

If you interrupt treatment with Sapropterin Dipharma

Do not interrupt treatment with Sapropterin Dipharma without first consulting your doctor, as this may increase blood phenylalanine levels.

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

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 have inflamed, red, and intensely itchy areas (urticaria), nasal discharge, rapid or irregular pulse, tongue or throat inflammation, sneezing, hissing while breathing, severe respiratory difficulty, or dizziness, you may be experiencing a severe allergic reaction to the medication. If you experience these symptoms, consult your doctor immediately.

Very Common Adverse Effects(may affect more than 1 in 10 people)

Headache and nasal discharge.

Common Adverse Effects(may affect up to 1 in 10 people)

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

Unknown Adverse Effects(cannot be estimated from the available data)

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the packaging and on the container after EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Sapropterin Dipharma

• The active ingredient is dihydrochloride of sapropterin.

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

Sapropterin Dipharma 500 mg:Each sachet contains 500 mg of dihydrochloride of sapropterin (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 packaging

The oral powder is of a color between white and yellowish. The powder is in single-dose sachets containing 100 mg or 500 mg of dihydrochloride of sapropterin.

Packaging of 30 sachets.

Marketing Authorization Holder

Dipharma Arzneimittel GmbH

Offheimer Weg 33

65549 Limburg a. d. Lahn

Germany

Responsible for manufacturing

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

Last revision date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan drugs.