PHEBURANE 350 MG/ML ORAL SOLUTION

Introduction

Package Leaflet: Information for the User

PHEBURANE 350 mg/mL Oral Solution

sodium phenylbutyrate

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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

Contents of the pack and other information

1. What PHEBURANE Oral Solution is and what it is used for
2. What you need to know before you take PHEBURANE
3. How to take PHEBURANE
4. Possible side effects
5. Storing PHEBURANE
6. Contents of the pack and other information

1. What PHEBURANE is and what it is used for

PHEBURANE contains the active substance sodium phenylbutyrate, which is used to treat patients with urea cycle disorders. These rare diseases are due to a deficiency of certain liver enzymes that are necessary to eliminate excess nitrogen in the form of ammonia.

Nitrogen is a basic component of proteins, which are an essential part of the food we eat. As the body breaks down proteins after eating, nitrogen residues accumulate in the form of ammonia because the body cannot eliminate them. Ammonia is especially toxic to the brain and leads, in severe cases, to low levels of consciousness and coma.

PHEBURANE helps the body eliminate excess nitrogen by reducing the amount of ammonia in the body. However, while taking PHEBURANE Oral Solution, you must follow a low-protein diet, specially designed for you by a doctor and a nutritionist. You must follow this diet strictly.

2. What you need to know before you take PHEBURANE

Do not take PHEBURANE:

• if you are allergic to sodium phenylbutyrate or any of the other ingredients of this medicine (listed in section 6).
• if you are pregnant.
• if you are breast-feeding.

Warnings and precautions

Consult your doctor or pharmacist before taking PHEBURANE if you:

• have congestive heart failure (a type of heart disease in which the heart cannot pump enough blood to the body) or decreased kidney function.
• have decreased kidney or liver function, as PHEBURANE Oral Solution is eliminated through the kidneys and liver.

PHEBURANE will not prevent the occurrence of acute ammonia excess in the blood, a situation that is usually a medical emergency. If this happens, you will develop symptoms such as feeling unwell (nausea), discomfort (vomiting), confusion, and you will need to seek urgent medical attention.

If you need laboratory tests, it is essential that you remind your doctor that you are taking PHEBURANE Oral Solution, as sodium phenylbutyrate may interfere with certain laboratory test results (such as electrolytes or proteins in blood, or liver function tests).

If you have any doubts, consult your doctor or pharmacist.

Other medicines and PHEBURANE

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

It is particularly important that you inform your doctor if you are taking medicines that contain:

• valproate (an antiepileptic medicine);
• haloperidol (used in certain psychotic disorders);
• corticosteroids (medicines used to relieve inflamed areas of the body);
• probenecid (for the treatment of hyperuricemia, high levels of uric acid in the blood associated with gout).

These medicines may alter the effect of PHEBURANE, and you will need to have blood tests more frequently. If you are not sure if your medicines contain these substances, consult your doctor or pharmacist.

Pregnancy and breast-feeding

Do not take PHEBURANE if you are pregnant, as this medicine may harm the fetus.

If you are a fertile woman, you must use safe contraceptive methods during treatment with PHEBURANE. Talk to your doctor for more details.

Do not use PHEBURANE if you are breast-feeding, as this medicine may pass into breast milk and may harm your baby.

Driving and using machines

It is unlikely that PHEBURANE Oral Solution will affect your ability to drive and use machines.

PHEBURANE Oral Solution contains sodium

This medicine contains 124 mg (5.4 mmol) of sodium (main component of common table salt) per dose of g of sodium phenylbutyrate. This is equivalent to 6.2% of the maximum recommended daily dietary intake of sodium for an adult.

The maximum daily dose of this medicine contains 2.5 g of sodium, which is equivalent to 125% of the maximum recommended daily dietary intake of sodium in an adult's diet.

Consult your doctor or pharmacist if you need to take 3 or more grams per day for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.

PHEBURANE Oral Solution contains aspartame

This medicine contains 5.7 mg of aspartame per dose of g of sodium phenylbutyrate. Aspartame is a source of phenylalanine. It may be harmful to you if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

The blackcurrant flavor coating contains propylene glycol

This medicine contains 26.55 mg of propylene glycol per drop.

If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, especially if the baby is taking other medicines that contain propylene glycol or alcohol.

3. How to take PHEBURANE Oral Solution

Always take this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you are not sure.

Dose

The daily dose of PHEBURANE Oral Solution will be based on your weight or body surface area and will be adjusted according to your tolerance to proteins and your diet. You will need to have regular blood tests to determine the correct daily dose. Your doctor will tell you how much liquid to take.

Method of administration

PHEBURANE Oral Solution should be taken with meals.

To measure a dose of PHEBURANE Oral Solution, you must use only the dosing syringe provided with PHEBURANE Oral Solution. Do not use other devices/spoons/syringes to administer a dose. The syringe has a graduation of 0.5 g to 3 g with increments of 0.25. The graduation of the dosing syringe reflects the grams of sodium phenylbutyrate. Follow these instructions to administer PHEBURANE Oral Solution:

Administration for oral use

1. Open the bottle of PHEBURANE Oral Solution by pushing the cap down and turning it to the left.

1. Remove the dosing syringe with the CE marking and the adapter for the bottle from the pouch.

1. Place (push) the adapter onto the neck of the bottle while the syringe is in the adapter.

1. Invert the bottle.

1. Withdraw the required amount of PHEBURANE Oral Solution (equivalent to the amount of grams of sodium phenylbutyrate prescribed by your doctor) using the dosing syringe.

1. Remove the dosing syringe with PHEBURANE Oral Solution from the adapter and pour the amount of PHEBURANE Oral Solution from the dosing syringe into a glass with at least 20 ml of water.

1. Close the bottle with PHEBURANE Oral Solution without removing the adapter inserted into the neck of the bottle.

1. Add one drop of the flavoring you like (blackcurrant or lemon-menthol) to the contents of the water glass; shake gently and drink (if one drop of flavoring does not provide the intensity of flavor you want, you can use 2 drops).

1. Wash the syringe only with cold to lukewarm water after each administration.

PHEBURANE Oral Solution should be taken with a special low-protein diet.

You must take PHEBURANE Oral Solution with each meal or food intake. In small children, it may be 4 to 6 times a day.

PHEBURANE Oral Solution can also be administered through nasogastric or gastrostomy tubes. PHEBURANE Oral Solution can be administered with tubes of a diameter of 2 mm (7-8 French) and larger. Use the supplied oral syringe to measure your dose and follow these instructions:

Preparation for administration through a nasogastric or gastrostomy tube

1. Follow steps 1 to 5 of the Method of administration for oral use;
2. PHEBURANE Oral Solution is ready to use and does not need to be diluted;
3. When using it through a nasogastric/gastrostomy tube, do not add the flavor coating;
4. Insert the tip of the syringe filled with the medicine into the tip of the nasogastric/gastrostomy tube;
5. Use the plunger of the dosing syringe to administer the prescribed dose of PHEBURANE Oral Solution into the nasogastric/gastrostomy tube;
6. The tube should be flushed once with the appropriate volume of warm water and allowed to drain after administration. In adults, 20 ml of warm water should be used. In children weighing less than 20 kg and neonates, 3 ml of water should be used.

You will need to take this medicine and follow a certain diet for the rest of your life.

If you take more PHEBURANE Oral Solution than you should

Patients who have taken very high doses of sodium phenylbutyrate have experienced the following:

• drowsiness, fatigue, dizziness, and confusion (less frequently);
• headache;
• changes in taste (alterations in taste);
• decreased hearing;
• disorientation;
• memory problems;
• worsening of existing neurological conditions.

If you experience any of these symptoms, you should immediately call your doctor or the emergency department of the nearest hospital to receive appropriate treatment.

If you forget to take PHEBURANE Oral Solution

You should take a dose as soon as possible with the next meal. Make sure that at least 3 hours pass between doses. Do not take a double dose to make up for the forgotten dose.

If you have any other doubts 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 everybody gets them.

If you experience persistent vomiting, you should contact your doctor immediately.

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

irregular menstrual periods and interruption of menstrual periods in fertile women.

If you are sexually active and your menstruation stops completely, do not assume it is due to PHEBURANE Oral Solution. If this happens, talk to your doctor, as the absence of menstruation may be due to pregnancy (see the "Pregnancy and breast-feeding" section above) or menopause.

Common side effects (may affect more than 1 in 100 people)

changes in blood cell count (red blood cells, white blood cells, and platelets), changes in blood bicarbonate levels, decreased appetite, depression, irritability, headache, fainting, fluid retention (swelling), changes in taste (alterations in taste), stomach pain, vomiting, nausea, constipation, abnormal skin odor, rash, abnormal kidney function, weight gain, alteration of laboratory test values.

Uncommon side effects (may affect more than 1 in 1,000 people)

red blood cell deficiency due to bone marrow failure, bruising, alteration of heart rhythm, rectal bleeding, stomach inflammation, stomach ulcer, pancreas inflammation.

Reporting of side effects

If you experience side effects, consult your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing PHEBURANE Oral Solution

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

Do not use PHEBURANE Oral Solution after the expiry date stated on the carton and on the label of the bottle after EXP. The expiry date refers to the last day of that month.

After opening the bottle of PHEBURANE Oral Solution for the first time, you must use the medicine within the next 4 weeks. The bottle should be discarded even if it is not empty.

After opening the flavoring bottle for the first time, you must use it within the next 4 weeks.

The bottle should be discarded even if it is not empty.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Packaging Contents and Additional Information

Composition of PHEBURANE Oral Solution

• The active ingredient is sodium phenylbutyrate. Each mL of liquid contains 350 mg of sodium phenylbutyrate
• The other ingredients are: purified water, aspartame (E951), sucralose (E955), glycerol (E422), hydroxyethylcellulose (E1525) (See section 2 "PHEBURANE oral solution contains aspartame").

Flavor Coatings:

• Blackcurrant flavor coating composed of blackcurrant and mint, which contains propylene glycol (E1520).
• Lemon-mint flavor coating composed of lemon and mint flavoring.

Appearance of PHEBURANE Oral Solution and Packaging Contents

PHEBURANE oral solution is a clear, colorless to pale yellow liquid.

Each package contains:

• A brown glass bottle containing 100 mL of the oral solution, which is closed with a child-resistant plastic cap;
• A dosing syringe with a range of 0.5 g to 3 g with increments of 0.25 for measuring the dose in grams of sodium phenylbutyrate;
• Bottle adapter;
• A brown glass bottle containing 3 mL of lemon-mint flavor coating;
• A brown glass bottle containing 3 mL of blackcurrant flavor coating.

Marketing Authorization Holder and Manufacturer

Eurocept International BV

Trapgans 5

1244 RL Ankeveen

Netherlands

To obtain any information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

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 medicines.