Label: Information for the User

PHEBURANE 350 mg/mL oral solution

sodium phenylbutyrate

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

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others 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 label. See section 4.

Contents of this label

1. What PHEBURANE oral solution is and for what it is used
2. What you need to know before starting to take PHEBURANE
3. How to take PHEBURANE
4. Possible adverse effects
5. Storage of PHEBURANE
6. Contents of the container and additional information

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

Nitrogen is a basic component of proteins, which are an essential part of the foods we ingest. As the body breaks down proteins after eating, residues of nitrogen 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 to eliminate residual nitrogen by reducing the amount of ammonia in your body. However, while taking PHEBURANE oral solution, you must have a low-protein diet, designed especially for you by a doctor and a nutritionist. You must strictly follow this diet.

Do not take PHEBURANE:

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take PHEBURANE if you:

• have congestive heart failure (a type of heart disease in which the heart cannot pump enough blood to the body) or a decrease in renal function.
• have a reduced renal or hepatic 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 occurs, you will develop symptoms such as a feeling of discomfort (nausea), discomfort (vomiting), confusion and you will need to obtain urgent medical help.

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

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

Other medications and PHEBURANE

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication.

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

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

These medications may alter the effect of PHEBURANE and you will need to have blood tests more frequently. If you are unsure whether your medications contain these substances, consult your doctor or pharmacist.

Pregnancy and lactation

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

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

Do not use PHEBURANE if you are breastfeeding, as this medication may reach the breast milk and may harm your baby.

Driving and operating machinery

It is unlikely that PHEBURANE oral solution will affect your ability to drive and operate machinery.

PHEBURANE oral solution contains sodium

This medication contains 124 mg (5.4 mmol) of sodium (the principal component of common salt or table salt) in each 1 g of sodium phenylbutyrate. This is equivalent to 6.2% of the maximum daily sodium intake recommended for an adult.

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

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

PHEBURANE oral solution contains aspartame

This medication contains 5.7 mg of aspartame per 1 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 medication 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 this medication, particularly if the baby is receiving other medications that contain propylene glycol or alcohol.

Take this medicine exactly as your doctor has told you to. If you are unsure, consult your doctor or pharmacist.

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 diet. You will need to have regular blood tests to determine the correct daily dose. Your doctor will tell you how much liquid you should 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 the instructions below to administer PHEBURANE oral solution:

Administration for oral use

1. Open the PHEBURANE oral solution bottle by pushing the cap down and turning it to the left.

1. Take out the dosing syringe with the CE marking and the bottle adapter from the package.

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

1. Invert the bottle.

1. Draw out of the bottle the required amount of PHEBURANE oral solution (equivalent to the prescribed amount of sodium phenylbutyrate in grams) using the dosing syringe.

1. Take out the dosing syringe with PHEBURANE oral solution from the adapter and pour the PHEBURANE oral solution from the dosing syringe into a glass with a minimum of 20 ml of water.

1. Close the PHEBURANE oral solution bottle without removing the adapter inserted into the bottle neck.

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

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

PHEBURANE oral solution should be taken with a special low-protein diet.

You should 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 oral syringe provided to measure your dose and follow the instructions below:

Preparation for administration through nasogastric or gastrostomy tube

1. Follow steps 1 to 5 of theMethod of administration for oral use;
2. PHEBURANE oral solution is ready for use and does not need to be diluted;
3. When using it through a nasogastric/gastrostomy tube,do not add the flavoring cover;
4. Insert the tip of the syringe filled with the medication 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 through the nasogastric/gastrostomy tube;
6. The tube should be washed once with the appropriate amount of warm water and should be 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 have to take this medicine and follow a specific 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 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 call your doctor or the emergency service of the nearest hospital immediately to receive the 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 have passed between the two doses. Do not take a double dose to make up for the dose you missed.

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

Like all medications, this medication may cause adverse effects, although not necessarily in all people.

If persistent vomiting occurs, contact your doctor immediately.

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

Irregular menstrual periods and cessation of menstrual periods in fertile women.

If you are sexually active and your menstruation is completely interrupted, do not assume it is due to PHEBURANE oral solution. If this occurs, discuss it with your doctor, as the absence of menstruation may be due to pregnancy (see the section “Pregnancy and breastfeeding” above) or menopause.

Frequent Adverse Effects(may affect more than 1 in 100 people)

Changes in the number of blood cells (red blood cells, white blood cells, and platelets), changes in the amount of bicarbonate in the blood, decreased appetite, depression, irritability, headaches, dizziness, 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.

Rare Adverse Effects(may affect more than 1 in 1,000 people)

Red blood cell deficiency due to bone marrow insufficiency, bruises, alteration of heart rhythm, rectal bleeding, stomach inflammation, stomach ulcer, pancreatitis.

Reporting Adverse Effects

If you experience side effects, consult your doctor or pharmacist. This includes any possible side effect not mentioned in this prospectus. You can also report side effects directly through thenational reporting system that appears in theAppendix V. Reporting side effects can help provide more information about the safety of this medication.

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

Do not use PHEBURANE oral solution after the expiration date indicated on the packaging and on the bottle label after CAD. The expiration date refers to the last day of that month.

When opening the PHEBURANE oral solution bottle for the first time, you must use the medication within the next 4 weeks. The bottle must be discarded even if it is not empty.

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

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

This medication does not require special storage conditions.

Do not dispose of any medication through household wastewater or trash. Ask your pharmacist how to dispose of unused medications. These measures will contribute to protecting the environment.

Active Ingredient Composition of PHEBURANE Oral Solution

• The active ingredient is phenylbutyrate sodium. Each mL of liquid contains 350 mg of phenylbutyrate sodium.
• 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-mint 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 Contents of the Container

PHEBURANE Oral Solution is a transparent, colorless to pale yellow liquid.

Each container contains:

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

Marketing Authorization Holder and Responsible Manufacturer

Eurocept International BV

Trapgans 5

1244 RL Ankeveen

Netherlands

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

Last Review Date of this Leaflet

For detailed information about this medicinal product, please visit the website of the European Medicines Agencyhttp://www.ema.europa.eu/.

There are also links to other websites about rare diseases and orphan medicines.