Ammonaps

Package leaflet: Information for the user

AMMONAPS 500 mg tablets

Sodium phenylbutyrate
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What AMMONAPS is and what it is used for

AMMONAPS is prescribed to patients with urea cycle disorders. Patients with this rare type of disorder have a deficiency in certain liver enzymes and are therefore unable to eliminate nitrogen waste. Nitrogen is a component of proteins, and thus, after protein intake, nitrogen accumulates in the body. Nitrogen waste, present in the form of ammonia, is particularly toxic to the brain and, in severe cases, may lead to decreased levels of consciousness up to coma.
AMMONAPS helps the body eliminate nitrogen waste by reducing the amount of ammonia in the body.

2. What you should know before taking AMMONAPS

Do not take AMMONAPS:

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

Warnings and precautions
Talk to your doctor before taking AMMONAPS

• if you have difficulty swallowing, because AMMONAPS tablets may get stuck in the oesophagus and cause ulcers. If you have difficulty swallowing, we recommend using AMMONAPS granules instead of tablets;
• if you have heart failure, reduced kidney function, or other conditions in which retention of sodium salt contained in this medicine may worsen your condition;
• if you have impaired liver or kidney function, as AMMONAPS is eliminated from the body through the kidneys and liver;
• in young children, as they may not be able to swallow the tablets and could therefore choke. It is recommended to use AMMONAPS granules instead of tablets.

AMMONAPS must be taken together with a low-protein diet specifically designed for you or your child by your doctor and dietitian. Follow this diet carefully.
AMMONAPS does not completely prevent acute episodes of high ammonia levels in the blood (hyperammonemia) and is not sufficient to treat this condition, which is a medical emergency.
If you need laboratory tests, it is important that you inform your doctor that you are taking AMMONAPS, as sodium phenylbutyrate may affect certain laboratory test results.

Other medicines and AMMONAPS
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 containing:

• valproic acid (an antiepileptic medicine),
• haloperidol (used in certain psychotic disorders),
• corticosteroids (medicines similar to cortisone used to relieve inflamed areas of the body),
• probenecid (for the treatment of hyperuricemia associated with gout).

These medicines may alter the effect of AMMONAPS, and therefore you may need to have blood tests more frequently. If you are unsure whether your medicines contain these substances, please check with your doctor or pharmacist.

Pregnancy and breastfeeding
Do not use AMMONAPS during pregnancy, as this medicine may harm the unborn baby. If you are a woman of childbearing age, you must use reliable contraceptive methods during treatment with AMMONAPS.
Do not use AMMONAPS while breastfeeding, as this medicine may pass into breast milk and harm the newborn baby.

Driving and using machines
No studies have been performed on the effects on the ability to drive vehicles or use machinery.

AMMONAPS contains sodium
Each AMMONAPS tablet contains 62 mg of sodium.
Inform your doctor or pharmacist if you need to take 6 or more tablets per day for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.

3. How to take AMMONAPS

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Dosage
Your daily dose of AMMONAPS will be calculated based on your protein tolerance, the diet you
follow, your body weight or body surface area. Regular blood tests will therefore be necessary to determine the exact daily dose. Your doctor will tell you how many tablets to take each day.
Method of administration
AMMONAPS is best taken orally in equally divided doses with each meal (e.g. three times a day). It is recommended to take AMMONAPS with a large amount of water.
Please remember that AMMONAPS must be taken in combination with a special low-protein diet.
AMMONAPS tablets must not be administered to children who are unable to swallow tablets. Therefore, the use of AMMONAPS granules is recommended.
You will need to continue this treatment and diet for life, unless you undergo a successful liver transplant.
If you take more AMMONAPS than you should
In patients who have taken very high doses of AMMONAPS, the following have been reported:

• drowsiness, fatigue, feeling of light-headedness and, less commonly, confusion,
• headache,
• altered taste sensation,
• hearing loss,
• disorientation,
• memory problems,
• worsening of pre-existing neurological conditions.

If any of these symptoms occur, contact your doctor or the nearest hospital emergency department immediately for supportive treatment.
If you forget to take AMMONAPS
Take the missed dose as soon as possible with your next meal. Make sure that at least 3 hours elapse between doses. Do not take a double dose to make up for the missed dose.
If you have any questions 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.
The following list indicates the frequency of possible side effects:
Very common: may occur in more than 1 in 10 people
Common: may occur in 1 to 10 in 100 people
Uncommon: may occur in 1 to 10 in 1,000 people
Rare: may occur in 1 to 10 in 10,000 people
Very rare: may occur in less than 1 in 10,000 people
Not known: cannot be estimated from the available data

Very common side effects: irregular menstrual cycles and absence of menstrual cycles. If you are sexually active and your periods stop completely, do not immediately assume this is due to AMMONAPS. Instead, discuss this with your doctor, as absence of menstruation may instead be caused by pregnancy (see section above on Pregnancy and breast-feeding).

Common side effects: changes in blood cell counts (red blood cells, white blood cells and platelets), loss of appetite, depression, irritability, headache, fainting, fluid retention (swelling), altered sense of taste, abdominal pain, vomiting, nausea, constipation, unusual odour of the skin, skin rash, abnormal kidney function, weight gain and abnormal laboratory test results.

Uncommon side effects: reduced red blood cells due to bone marrow suppression, bruising, altered heart rhythm, rectal bleeding, gastric irritation, gastric ulcer, inflammation of the pancreas.

If vomiting persists, contact your doctor or pharmacist immediately.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store AMMONAPS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the
vial after "Exp.". The expiry date refers to the last day of the month.
Do not store above 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What AMMONAPS contains

• The active substance is sodium phenylbutyrate. Each AMMONAPS tablet contains 500 mg of sodium phenylbutyrate.
• The other components are microcrystalline cellulose, magnesium stearate and anhydrous colloidal silicon dioxide.

Description of the appearance of AMMONAPS and package contents
AMMONAPS tablets are white, oval-shaped and engraved with the code "UCY 500".
The tablets are packaged in plastic bottles with child-resistant caps. Each bottle contains 250 or 500 tablets.
Marketing Authorization Holder
Immedica Pharma AB
SE-113 29 Stockholm
Sweden
Manufacturer
PATHEON France – BOURGOIN JALLIEU
40 boulevard de Champaret
BOURGOIN JALLIEU
France
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Package leaflet: information for the user

AMMONAPS 940 mg/g granules

Sodium phenylbutyrate
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What AMMONAPS is and what it is used for

AMMONAPS is prescribed to patients with urea cycle disorders. Patients with this rare type of disorder have a deficiency in certain liver enzymes and therefore are unable to eliminate nitrogen waste. Nitrogen is a component of proteins, and thus, after protein intake, nitrogen accumulates in the body. Nitrogen waste, present in the form of ammonia, is particularly toxic to the brain and, in severe cases, may lead to decreased levels of consciousness up to coma.
AMMONAPS helps the body eliminate nitrogen waste by reducing the amount of ammonia present in the body.

2. What you need to know before taking AMMONAPS

Do not take AMMONAPS:

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

Warnings and precautions
Talk to your doctor before taking AMMONAPS

• if you have heart failure, reduced kidney function, or other conditions in which retention of the sodium salt contained in this medicine may worsen your condition;
• if you have impaired liver or kidney function, since AMMONAPS is eliminated from the body through the kidneys and liver.

AMMONAPS must be taken together with a specially designed low-protein diet prescribed for you or your child by the doctor and dietitian. Carefully follow this diet.
AMMONAPS does not completely prevent the occurrence of acute episodes of elevated blood ammonia levels (hyperammonemia) and is not sufficient for the treatment of this condition, which is a medical emergency.
If you are undergoing laboratory tests, it is important that you inform your doctor that you are taking AMMONAPS, as sodium phenylbutyrate may affect certain laboratory test results.
Other medicines and AMMONAPS
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is especially important that you inform your doctor if you are taking medicines containing:

• valproic acid (an antiepileptic medicine),
• haloperidol (used in certain psychotic disorders),
• corticosteroids (medicines similar to cortisol, used to relieve inflamed areas of the body),
• probenecid (for the treatment of hyperuricemia associated with gout).

These medicines may alter the effect of AMMONAPS, and you may require more frequent blood tests. If you are unsure whether your medicines contain these substances, please check with your doctor or pharmacist.
Pregnancy and breastfeeding
Do not use AMMONAPS during pregnancy, as this medicine may harm the fetus. If you are a woman of childbearing age, you must use reliable contraceptive methods during treatment with AMMONAPS.
Do not use AMMONAPS while breastfeeding, as this medicine may pass into breast milk and harm the newborn.
Driving and use of machines
No studies have been conducted on the effects on the ability to drive vehicles or operate machinery.
AMMONAPS contains sodium
One small white scoop of AMMONAPS granules contains 149 mg of sodium.
One medium yellow scoop of AMMONAPS granules contains 408 mg of sodium.
One large blue scoop of AMMONAPS granules contains 1200 mg of sodium.
Inform your pharmacist or doctor if you need to take 2 or more small white scoops or 1 or more medium yellow or large blue scoops daily over a prolonged period, especially if you have been advised to follow a low-salt (low-sodium) diet.

3. How to take AMMONAPS

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

Dosage
Your daily dose of AMMONAPS will be calculated based on your protein tolerance, the diet you follow, your body weight or body surface area. Regular blood tests will therefore be necessary to determine the correct daily dose. Your doctor will tell you how much granules to take each day.

Method of administration
AMMONAPS is recommended to be taken orally or via gastrostomy (a tube from the abdomen into the stomach) or through a nasogastric tube (a tube from the nose into the stomach), divided into equal doses.

AMMONAPS must be taken together with a low-protein diet.

Administer AMMONAPS with each meal or feeding. For young children, the frequency may be from 4 to 6 times per day.

To measure the dose:

• Gently shake the bottle before opening.
• Use the appropriate measuring scoop to administer the following amounts of Ammonaps: 1.2 g = small white scoop; 3.3 g = medium yellow scoop; 9.7 g = large blue scoop.
• Completely fill the scoop with granules taken directly from the bottle.
• Level off the scoop with a flat surface, such as the bottom edge of a knife, to remove excess granules.
• The amount of granules remaining in the scoop corresponds to one tablespoon.
• Take the correct number of tablespoons of granules from the bottle.

For oral administration
Mix the dose with solid foods (e.g., mashed potatoes or apple sauce) or with liquid foods (e.g., water, apple juice, orange juice, or protein-free infant formulas), and swallow immediately after mixing.

For patients using gastrostomy or nasogastric tube
Dissolve the granules in water until no dry powder remains (shaking the solution is recommended to facilitate dissolution). When dissolved in water, the granules form a white, milky liquid. Drink the solution immediately after mixing.

You will need to continue this treatment and follow a special diet for life, unless you undergo a successful liver transplant.

If you take more AMMONAPS than you should
In patients who have taken very high doses of AMMONAPS, the following have been reported:

• Drowsiness, fatigue, lightheadedness, and less commonly, confusion,
• Headache,
• Altered taste sensation,
• Hearing loss,
• Disorientation,
• Memory problems,
• Worsening of pre-existing neurological conditions.

If any of these symptoms occur, contact your doctor or the nearest hospital emergency department immediately for supportive treatment.

If you forget to take AMMONAPS
Take the missed dose as soon as possible with your next meal. Make sure that at least 3 hours elapse between doses. Do not take a double dose to make up for the forgotten dose.

If you have any doubts about how to use 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.
The frequency of possible side effects is listed below:
Very common: may occur in more than 1 in 10 people
Common: may occur in 1 to 10 in 100 people
Uncommon: may occur in 1 to 10 in 1,000 people
Rare: may occur in 1 to 10 in 10,000 people
Very rare: may occur in fewer than 1 in 10,000 people
Not known: cannot be estimated from the available data

Very common side effects: irregular menstrual cycles and absence of menstrual cycles. If you are sexually active and your periods stop completely, do not immediately assume this is due to AMMONAPS. Instead, discuss this with your doctor, as absence of menstruation could be caused by pregnancy (see the section above on Pregnancy and breast-feeding).

Common side effects: changes in blood cell counts (red blood cells, white blood cells and platelets), loss of appetite, depression, irritability, headache, fainting, fluid retention (swelling), altered sense of taste, abdominal pain, vomiting, nausea, constipation, unusual odour of the skin, rash, abnormal kidney function, weight gain and abnormal laboratory test results.

Uncommon side effects: reduced red blood cells due to bone marrow suppression, bruising, altered heart rhythm, rectal bleeding, gastric irritation, gastric ulcer, inflammation of the pancreas.

If vomiting persists, contact your doctor or pharmacist immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store AMMONAPS

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of the month.
Do not store above 25°C.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What AMMONAPS contains

• The active substance is sodium phenylbutyrate. One gram of AMMONAPS granules contains 940 mg of sodium phenylbutyrate.
• The other components are calcium stearate and anhydrous colloidal silica.

Description of the appearance of AMMONAPS and contents of the pack
AMMONAPS granules are white to off-white in colour.
The granules are packed in plastic bottles with child-resistant caps. Each bottle contains
266 g or 532 g of granules. Three measuring scoops (one small white, one medium yellow and one
large blue) are included to measure the daily dose.
Marketing Authorisation Holder
Immedica Pharma AB
SE-113 29 Stockholm
Sweden
Manufacturer
PATHEON France – BOURGOIN JALLIEU
40 boulevard de Champaret
BOURGOIN JALLIEU
France
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu