Kuvan 100 mg, dispersible tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Kuvan 100 mg dispersible tablets

sapropterin dihydrochloride

Read all of this 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 others, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Kuvan is and what it is used for

2. What you need to know before taking Kuvan

3. How to take Kuvan

4. Possible side effects

5. How to store Kuvan

6. Contents of the pack and other information

1. What Kuvan is and what it is used for

Kuvan contains the active substance sapropterin, which is a synthetic copy of a substance naturally present 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.

Kuvan 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, which can be harmful. Kuvan 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, which have harmful effects. By replacing the BH4 that the body cannot produce, Kuvan reduces the harmful excess of phenylalanine in the blood and increases dietary phenylalanine tolerance.

2. What you need to know before taking Kuvan

Do not take Kuvan

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 Kuvan, 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 your doctor during illness, as blood phenylalanine levels may increase

• if you are predisposed to seizures

While receiving treatment with Kuvan, your doctor will perform blood tests to monitor your levels of phenylalanine and tyrosine, and will decide whether dose adjustments of Kuvan or dietary changes are necessary.

You must continue your dietary treatment as recommended by your doctor. Do not change your diet without informing your doctor. Even when taking Kuvan, 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 Kuvan, to ensure that they are neither too high nor too low.

Use of Kuvan 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 used to treat cancer (e.g., methotrexate)
• medicines used to treat 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 may 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 control your phenylalanine levels. If these levels are not strictly controlled before or at the start of 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 using machines

Kuvan is not expected to affect your ability to drive or operate machinery.

Important information about some of the ingredients of Kuvan

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; i.e., essentially “sodium-free”.

3. How to take Kuvan

Follow exactly the administration instructions for this medicine as indicated by your doctor.

If in doubt, consult your doctor again.

Dosage for PKU

The recommended initial dose of Kuvan in patients with PKU is 10 mg per kg of body weight. Take Kuvan once daily with a meal to increase absorption, 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, depending on your condition.

Dosage for BH4 deficiency

The recommended initial dose of Kuvan in patients with BH4 deficiency is 2 to 5 mg per kg of body weight. Take Kuvan with a meal to increase 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 daily per kg of body weight, 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 all patients

Place the prescribed tablets into a glass or cup of water, exactly as described below, and stir until they dissolve.

The tablets may take a few minutes to dissolve. To speed up dissolution, you may crush them. Small particles may be visible in the solution, but these will not affect the effectiveness of the medicine. Drink the dissolved Kuvan preparation with a meal within 15 to 20 minutes after preparation.

Do not ingest the capsule containing the desiccant included in the bottle.

Use in patients with body weight above 20 kg

Place the tablets into 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 advise you:

• the number of Kuvan tablets required for a dose
• the amount of water needed to mix a dose of Kuvan
• the volume of solution to administer to the child for the prescribed dose

The child must drink the Kuvan solution with a meal.

Administer the prescribed volume of solution to the child within 15 to 20 minutes after dissolving the tablets. If you are unable to administer the dose to the child within 15 to 20 minutes after dissolving the tablets, you must prepare a fresh solution, as unused solution must not be used after 20 minutes.

Materials required to prepare and administer the Kuvan dose to the child

• The number of Kuvan tablets required for a dose
• An oral 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 syringe for administering volumes ≤10 ml or a 20 ml syringe for volumes >10 ml)

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

Steps for preparing and administering the dose:

• Place the prescribed tablets into the dosing cup. Pour into the dosing cup the amount of water indicated by your doctor (e.g., your doctor may have instructed you to use 20 ml to dissolve one Kuvan tablet). Check that the liquid level aligns (at the corresponding graduation mark on the dosing cup) with the amount specified by your doctor. Stir with a clean spoon or utensil until the tablets dissolve completely.

• If your doctor has instructed you to administer only a portion of the solution, insert the tip of the oral dosing syringe into the dosing cup. Slowly pull back the plunger to withdraw the volume specified 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 dispensed into the glass or cup (e.g., if your doctor instructed you to dissolve two Kuvan tablets 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 cup). Use a 10 ml oral syringe for volumes ≤10 ml or a 20 ml oral syringe for volumes >10 ml.

• If the infant 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 infant’s mouth. Direct the tip of the syringe toward one of the cheeks. Slowly push the plunger so that a small amount is released at a time, until the entire solution in the syringe has been administered.

• Discard any remaining unused solution. Remove the plunger from the body of the oral dosing syringe. Wash both parts of the oral dosing syringe and the dosing cup with warm water and allow them to air dry. Once the oral dosing syringe is dry, reinsert the plunger into the syringe barrel. Store the oral dosing syringe and dosing cup for future use.

If you take more Kuvan than you should

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

If you forget to take Kuvan

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

If you stop taking Kuvan

Do not stop treatment with Kuvan 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 everybody will experience them.

A small number of cases of allergic reactions (such as skin rashes and severe reactions) have been reported.

Their frequency is unknown (frequency cannot be estimated from the available data).

If you develop inflamed, red and intensely itchy 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 severe allergic reaction to the medicine. If you experience 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 discomfort (nausea) (see section 2: "Warnings and precautions").

Adverse effects frequency not known (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 listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Kuvan

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 outer packaging, following EXP. The expiry date refers to the last day of the month indicated.

Store below 25 °C.

Keep the bottle tightly closed to protect it from moisture.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of any unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Kuvan

• 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), calcium hydrogen phosphate anhydrous, crospovidone type A, ascorbic acid (E300), sodium stearyl fumarate, and riboflavin (E101).

Appearance of the product and contents of the pack

Kuvan 100 mg dispersible tablets are white to pale yellow in colour, marked with "177" on one side.

They are supplied in bottles with child-resistant safety closures containing 30, 120 or 240 dispersible tablets. Each bottle contains a small plastic tube with desiccant (silica gel).

Only certain pack sizes may be marketed.

Marketing Authorization Holder

BioMarin International Limited
Shanbally, Ringaskiddy
County Cork
Ireland

Manufacturer

BioMarin International Limited
Shanbally, Ringaskiddy
County Cork
Ireland

Date of the most recent review of this summary: {MM/YYYY} Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also provided.