PHEBURANE 483 mg/g GRANULES

Introduction

Leaflet:information for the user

PHEBURANE 483mg tablets

Sodium phenylbutyrate

Read this leaflet carefully before starting to take this medicine, as 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 to you only, 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 side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What is PHEBURANE and what is it used for
2. What you need to know before taking PHEBURANE
3. How to take PHEBURANE
4. Possible side effects
5. Storage of PHEBURANE
6. Package contents and additional information

1. What is PHEBURANE and what is it used for

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

Nitrogen is a component of proteins, which are an essential part of the food we eat. As the body breaks down proteins after eating, residual nitrogen, in the form of ammonia, accumulates because the body cannot eliminate it. Ammonia is particularly toxic to the brain and, in severe cases, can cause loss of consciousness and coma.

PHEBURANE helps the body eliminate residual nitrogen and reduces the amount of ammonia in the body.

However, PHEBURANE must be used with a low-protein diet, which your doctor or dietitian has specifically developed for your case. You should follow this diet carefully.

2. What you need to know before taking PHEBURANE

Do not take PHEBURANE:

• if you are allergic to sodium phenylbutyrate or any of the other components of this medicine (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 heart failure (a type of heart disease in which the heart cannot pump enough blood for the body) or decreased kidney function
• have decreased kidney or liver function, as PHEBURANE is eliminated from the body by these organs.

PHEBURANE does not completely prevent excess ammonia from occurring in the blood, a condition that is usually a medical emergency. If this happens, you will experience symptoms such as nausea, vomiting, confusion, and you should receive urgent medical attention.

If you need to have tests, it is important to remind your doctor that you are taking PHEBURANE, as sodium phenylbutyrate may interfere with the results of some tests (such as electrolytes or proteins in the blood, or liver function tests).

In case of any doubt, consult your doctor or pharmacist.

Other medicines and PHEBURANE

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

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

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

These medicines may modify the effect of PHEBURANE, and you should have blood tests more frequently. If you are not sure if the medicines you are using contain these active substances, consult your doctor or pharmacist.

Pregnancy and breastfeeding

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

In case you may become pregnant, you must use an effective contraceptive method during treatment with PHEBURANE. Consult your doctor for details.

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

Driving and using machines

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

PHEBURANE contains sodium and sucrose.

This medicine contains 124 mg (5.4 mmol) of sodium per 1 g of sodium phenylbutyrate. Talk to 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-salt (sodium) diet.

This medicine contains 768 mg of sucrose per 1 g of sodium phenylbutyrate. This should be taken into account if you have diabetes mellitus. If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take PHEBURANE

Follow the administration instructions for this medicine exactly as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Dosage

The daily dose of PHEBURANE will be based on your body weight or body surface area and will be adjusted according to your tolerance to proteins and diet. You should have regular blood tests to adjust the correct daily dose. Your doctor will tell you the amount to take.

Method of administration

PHEBURANE should be taken orally. Because it dissolves slowly, PHEBURANE should not be administered through a gastrostomy (a tube that goes to the stomach through the abdomen) or through a nasogastric tube (a tube that goes to the stomach through the nose).

PHEBURANE should be taken while following a special low-protein diet.

You should take PHEBURANE with each meal. In young children, this may be 4 to 6 times a day.

The doses of PHEBURANE prescribed by your doctor are expressed in grams of sodium phenylbutyrate. This medicine includes a calibrated measuring spoon that dispenses up to 3 g of sodium phenylbutyrate at a time. Use this measuring spoon only to measure the dose of PHEBURANE. The measuring spoon should not be used for any other medicine.

To measure the dose:

• The lines on the measuring spoon indicate the amount of PHEBURANE in grams of sodium phenylbutyrate. Take the correct amount as prescribed by your doctor.
• Pour the granules directly into the measuring spoon as shown in the picture (on the outer box and in this leaflet).

• Gently tap the measuring spoon once to get a horizontal level of granules and continue filling if necessary.

The granules can be swallowed directly with a drink (water, fruit juice, protein-free infant formulas), or they can be added to a spoonful of solid food (mashed potatoes or apple sauce). If you mix it with food, it is important to take it immediately. This will help preserve the flavor masking.

You will need to take this medicine and follow a diet for life.

If you take more PHEBURANE than you should

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

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

If you experience any of these symptoms, you should contact your doctor or the emergency department of the nearest hospital immediately for symptomatic treatment.

If you forget to take PHEBURANE

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If persistent vomiting occurs, you should call your doctor immediately.

Very common side effects (may affect more than 1 in 10 people): irregular menstrual periods and cessation of menstruation in fertile women.

It is possible that the absence of menstruation in sexually active women is not caused by the use of PHEBURANE. If this happens, consult your doctor, as it could be caused by pregnancy (see "Pregnancy and breastfeeding" in the previous section) 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 (taste disorders), abdominal pain, vomiting, nausea, constipation, body odor, rash, abnormal kidney function, weight gain, alteration of test results.

Uncommon side effects (may affect more than 1 in 1,000 people): low red blood cell count (anemia) due to bone marrow failure, bruising, irregular heartbeat, rectal bleeding, stomach inflammation, gastroduodenal ulcer, pancreatitis.

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of PHEBURANE

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

Do not use PHEBURANE after the expiration date stated on the box and label of the bottle after "EXP". The expiration date is the last day of the month indicated.

After opening for the first time, PHEBURANE can be used for 45 days.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and additional information

Composition of PHEBURANE

The active substance is sodium phenylbutyrate

Each gram of granules contains 483 mg of sodium phenylbutyrate.

The other ingredients are: sugar spheres (sucrose and cornstarch, see section 2 "PHEBURANE contains sucrose"), hypromellose, ethylcellulose N7, macrogol 1500, povidone K25.

Appearance and package contents

PHEBURANE granules are white to off-white.

The granules are packaged in a plastic bottle with a child-resistant closure and a desiccant. Each bottle contains 174 g of granules. Each box contains one bottle.

It includes a calibrated measuring spoon.

Marketing authorization holder and manufacturer

Eurocept International BV

Trapgans 5

1244 RL Ankeveen

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Detailed information on this medicine 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.