Sapropterin Dihydrochloride 100 mg Soluble tablet

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• Sapropterin dihydrochloride soluble tablets have been prescribed for you only. Do not pass them on to others. They may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Sapropterin dihydrochloride soluble tablets are and what they are used for
2. What you need to know before you use Sapropterin dihydrochloride soluble tablets
3. How to use Sapropterin dihydrochloride soluble tablets
4. Possible side effects
5. How to store Sapropterin dihydrochloride soluble tablets
6. Contents of the pack and other information

If you are allergic to sapropterin or any of the other ingredients of Sapropterin dihydrochloride soluble tablets (listed in section 6).

Talk to your doctor or pharmacist before taking Sapropterin dihydrochloride soluble tablets, particularly:

• if you are 65 years of age or older
• if you have problems with your kidney or liver
• if you are ill. Consultation with a physician is recommended during illness as blood phenylalanine levels may increase
• if you have a predisposition to convulsions.

When you are treated with Sapropterin dihydrochloride soluble tablets, your doctor will test your blood to verify how much phenylalanine and tyrosine it contains and may decide to adjust the dose of Sapropterin dihydrochloride soluble tablets or your diet if needed.

You must continue your diet treatment as recommended by your doctor. Do not change your diet without contacting your doctor. Even if you take Sapropterin dihydrochloride soluble tablets, if your phenylalanine blood levels are not well controlled, you can develop severe neurological problems. Your doctor should continue to monitor your blood phenylalanine levels often during your treatment with Sapropterin dihydrochloride soluble tablets, to make sure that your blood phenylalanine levels are not too high or too low.

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 (used to treat Parkinson’s disease)
• medicines for treatment of cancer (e.g. methotrexate)
• medicines for treatment of bacterial infections (e.g. trimethoprim)
• medicines that cause dilation of blood vessels (such as glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), sodium nitroprusside (SNP), molsidomin, minoxidil).

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking Sapropterin dihydrochloride soluble tablets.

If you are pregnant your doctor will tell you how to control phenylalanine levels adequately. If these are not strictly controlled before or when you become pregnant, this could be harmful to you and to your baby. Your doctor will monitor the restriction of dietary phenylalanine intake prior and during pregnancy.

If the strict diet does not adequately reduce the phenylalanine amount in your blood your doctor will consider whether you must take Sapropterin dihydrochloride soluble tablets.

You should not take Sapropterin dihydrochloride soluble tablets if you are breast-feeding.

Sapropterin dihydrochloride soluble tablets are not expected to affect the ability to drive and use machines.

Sapropterin dihydrochloride soluble tablets contain less than 1 mmol sodium (23mg) per tablet, that is to say essentially ‘sodium-free’.

The recommended starting dose of Sapropterin dihydrochloride soluble tablets in patients with PKU is 10mg for each kg of body weight. Take Sapropterin dihydrochloride soluble tablets as a single daily dose with a meal to increase the absorption, and at the same time each day, preferably in the morning. Your doctor may adjust your dose, usually between 5 and 20mg for each kg of body weight per day, depending on your condition.

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

Example of how an appropriate dose is calculated

Body weight: 10kg Number of 100mg tablets (dose 10mg/kg): 1 Number of 100 mg tablets (dose 20mg/kg): 2

Body weight: 20kg Number of 100mg tablets (dose 10mg/kg): 2 Number of 100 mg tablets (dose 20mg/kg): 4

Body weight: 30kg Number of 100mg tablets (dose 10mg/kg): 3 Number of 100 mg tablets (dose 20mg/kg): 6

Body weight: 40kg Number of 100mg tablets (dose 10mg/kg): 4 Number of 100 mg tablets (dose 20mg/kg): 8

Body weight: 50kg Number of 100mg tablets (dose 10mg/kg): 5 Number of 100 mg tablets (dose 20mg/kg): 10

For PKU patients, the total daily dose is taken once a day at the same time each day, preferably in the morning.

For BH4 deficiency patients, the total daily dose is divided into 2 or 3 doses over the day.

Use in all patients

Place the prescribed number of tablets in a glass or cup of water as accurately described below and stir until dissolved.

It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster you can crush them. Small particles may be visible in the solution, but they will not affect the effectiveness of the medicine. Drink the dissolved preparation with a meal within 15 to 20 minutes of its preparation. Do not swallow the desiccant capsule contained in the bottle.

Use in patients above 20kg body weight

Place the tablets in a glass or cup (120 to 240ml) of water and stir until dissolved.

Use in children up to 20kg body weight

The dose is based on body weight. This will change as your child grows. Your doctor will tell you:

• the number of Sapropterin dihydrochloride soluble tablets needed for one dose
• the amount of water needed to mix one dose of Sapropterin dihydrochloride soluble tablets
• the amount of solution you will need to give your child for their prescribed dose.

Your child should drink the solution with a meal.

Give your child the prescribed amount of solution within 15 to 20 minutes after dissolving. If you are not able to give your child’s 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 beyond 20 minutes.

Supplies needed to prepare and give your child’s dose of Sapropterin dihydrochloride soluble tablets

• The number of Sapropterin dihydrochloride soluble tablets needed for one dose.
• A medicine cup with graduation markings at 20, 40, 60 and 80ml.
• A glass or cup.
• Small spoon or clean utensil for stirring.
• Oral syringe (graduated in 1ml divisions) (10ml syringe for administration of volumes of ≤ 10ml or 20ml syringe for administration of volumes of > 10ml).

Ask your doctor for the medicine cup for dissolving the tablets and the 10ml or 20ml oral syringe if you do not have these supplies.

Steps for preparing and taking your dose:

• Place the prescribed number of tablets in the medicine cup. Pour the amount of water into the medicine cup, as instructed by your doctor (e.g. your doctor told you to use 20ml for dissolving one tablet). Check to make sure that the amount of liquid lines up with the amount that your doctor tells you. Stir with the small spoon or clean utensil until the tablets dissolve.
• If your doctor told you to administer only a portion of the solution, point the tip of the oral syringe into the medicine cup. Slowly pull back the plunger to withdraw the amount as instructed by your doctor.
• Transfer the solution by pushing on the plunger slowly until all of the solution in the oral syringe is transferred to a glass or cup for administration (e.g. if your doctor told you to dissolve two tablets in 40ml water and administer 30ml to your child, you would have to use the 20ml oral syringe two times to draw up 30ml (e.g. 20ml + 10ml) of the solution and transfer it to a glass or cup for administration). Use a 10ml oral syringe for administration of volumes ≤10ml or a 20ml oral syringe for administration of volumes >10ml.
• If your baby is too small to drink from a glass or a cup you may administer the solution via the oral syringe. Draw up the prescribed volume from the solution prepared in the medicine cup and place the tip of the oral syringe into your baby’s mouth. Point the tip of the oral syringe towards either cheek. Push on the plunger slowly, a small amount at a time, until all of the solution in the oral syringe is given.
• Throw away any remaining solution. Remove the plunger from the barrel of the oral syringe. Wash both parts of the oral syringe and the medicine cup with warm water and air dry. When the oral syringe is dry, put the plunger back into the barrel. Store the oral syringe and the medicine cup for next use.

If you take more of Sapropterin dihydrochloride soluble tablets than prescribed, you may experience side effects that could include headache and dizziness. Immediately contact your doctor or pharmacist if you take more Sapropterin dihydrochloride soluble tablets than prescribed.

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

Do not stop taking Sapropterin dihydrochloride soluble tablets without prior discussion with your doctor, as phenylalanine levels in your blood may increase.

If you get 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is sapropterin dihydrochloride. Each soluble tablet contains 100mg of sapropterin dihydrochloride (equivalent to 77mg of sapropterin).
• The other ingredients are mannitol (E421), calcium hydrogen phosphate, crospovidone type A, ascorbic acid (E300), riboflavin (E101), sodium stearyl fumarate.

Sapropterin dihydrochloride soluble tablets are off white to light yellow, mottled, round shaped tablets, debossed with ‘ZS’ on one side and plain on other side.

Sapropterin dihydrochloride soluble tablets are available in a HDPE container with child-resistant closure of 120 soluble tablets. Each bottle contains silica gel as desiccant and polyester coil to fill the void in the container.