AMMONAPS 500 mg tabletsPatient’s LeafletSummary for the publ - United Kingdom[英国药品]

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AMMONAPS 500 mg tabletsPatient’s LeafletSummary for the publ

2014-02-18 21:30:40 来源: 作者: 【大中小】浏览:416次评论:0条

For doctors

What is it and how is it used?

AMMONAPS is prescribed to patients with urea cycle disorders. Patients with these rare disorders have a deficiency of certain liver enzymes and are therefore unable to eliminate nitrogen waste. Nitrogen is a building block of proteins, because of this, there is a build up of nitrogen in the body after eating protein. Nitrogen waste, in the form of ammonia, is especially toxic for the brain and leads, in severe cases, to reduced levels of consciousness and to coma.

AMMONAPS helps the body to eliminate nitrogen waste, reducing the amount of ammonia in your body.

What do you have to consider before using it?

Do not take AMMONAPS if you:

Take special care with AMMONAPS

AMMONAPS must be combined with a diet reduced in proteins designed especially for you by the doctor and the dietician. You must follow this diet carefully.

AMMONAPS does not completely prevent the occurrence of an acute excess of ammonia in the blood and is not appropriate for treating such a condition, which is a medical emergency.

If you require laboratory tests, it is important to remind your doctor that you are taking AMMONAPS, since sodium phenylbutyrate may influence certain laboratory test results.

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

It is especially important to tell your doctor if you are taking medicines containing:

These medicines may change the effect of AMMONAPS and you will need more frequent blood controls. If you are uncertain if your medicines contain these substances, you should check with your doctor or pharmacist.

Pregnancy and breast-feeding
Do not use AMMONAPS if you are pregnant, because this medicine can harm your unborn baby. If you are a woman who could get pregnant, you must use reliable contraception, during treatment with AMMONAPS.
Do not use AMMONAPS if you are breast-feeding, because this medicine can pass into the breast-milk and harm your baby.

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

Important information about some of the ingredients of AMMONAPS
Each AMMONAPS tablet contains 62 mg of sodium. To be taken into consideration by patients on a sodium controlled diet.

How is it used?

Always take AMMONAPS exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Dosage
The daily dose of AMMONAPS will be calculated from your protein tolerance, diet and body weight or body surface. You will need regular blood tests to determine the correct daily dose. Your doctor will tell you how many tablets you should take.

Method of administration
You should take AMMONAPS by mouth in equally divided doses with each meal (for example three times per day).You should take AMMONAPS with a large volume of water.

AMMONAPS must be taken with a special diet reduced in protein.

AMMONAPS tablets should not be given to children who are not able to swallow tablets. It is recommended that AMMONAPS granules are used instead.

You will need to have treatment and to follow a diet throughout your life, unless you have a successful liver transplantation.

If you take more AMMONAPS than you should
Patients who have taken very high doses of AMMONAPS experienced:

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

If you forget to take AMMONAPS
You should take a dose as soon as possible with your next meal. Make sure that there are at least 3 hours between two doses. Do not take a double dose to make up for a forgotten dose.

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

What are possible side effects?

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

The frequency of possible side effects is listed below.

Very common Common Uncommon Rare Very rare Not known Affects more than 1 user in 10 Affects 1 to 10 users in 100 Affects 1 to 10 users in 1,000 Affects 1 to 10 users in 10,000 Affects less than 1 user in 10,000 Frequency cannot be estimated from the available data

Very common side effects: irregular menstrual periods and cessation of menstrual periods. If you are sexually active and your period stops altogether, do not assume that this is caused by AMMONAPS. If this occurs, please discuss it with your doctor, because the absence of your period may be caused by pregnancy (see Pregnancy and breast-feeding section above).

Common side effects: changes in number of blood cells (red cells, white cells and platelets), reduced appetite, depression, irritability, headache, fainting, fluid retention (swelling), changes in taste (taste disturbances),pain in the abdomen, vomiting, nausea, constipation, skin odour, rash, abnormal kidney function, weight gain, altered laboratory test values.

Uncommon side effects: deficiency in red blood cells due to bone marrow depression, bruising, altered heart rhythm, rectal bleeding, stomach irritation, stomach ulcer, inflammation of the pancreas.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

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

How should it be stored?

Keep out of the reach and sight of children.

Do not use AMMONAPS after the expiry date which is stated on the carton and the bottle label after “EXP”. The expiry date refers to the last day of that month.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

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For doctors

What is it?

Ammonaps is a medicine that contains the active substance sodium phenylbutyrate. It is available as white oval tablets (500 mg) and as granules (940 mg/g).

What is it used for?

Ammonaps is used to treat patients who have urea cycle disorders. These patients are not able to get rid of waste nitrogen from the body because they lack some enzymes that are usually found in the liver. In the body, waste nitrogen is in the form of ammonia, which is toxic, especially for the brain. Ammonaps is used in patients who lack one or more of the following enzymes: carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase. It can be used in patients with the following forms of the disease:
• ‘early-onset’ disease in babies who show a complete lack of one or more of these enzymes within the first month of life;
• ‘late-onset’ disease in patients who show a partial lack of an enzyme after the age of one month and have had brain damage caused by high blood ammonia levels.
The medicine can only be obtained with a prescription.

How is it used?

Ammonaps treatment should be supervised by a doctor who has experience in treating patients with urea cycle disorders.
Ammonaps is used as an add-on to other treatments and with a special low-protein diet to reduce the intake of nitrogen. The daily dose of Ammonaps is adjusted for each patient individually and depends on the patient’s diet, height and weight. Regular blood tests are needed to find the correct daily dose. The dose of Ammonaps should be divided into equal amounts and given with each meal. The tablets are for adults and children, and the granules are used in babies and in patients who cannot swallow tablets. The granules are either mixed into food or drink immediately before being taken, or dissolved in water before being given through a tube leading through the tummy or nose to the stomach.
Ammonaps is a long-term treatment and needs to be taken until the patient has a successful liver transplant.

How does it work?

Eating protein brings nitrogen into the body, which is then transformed into ammonia. Patients with urea cycle disorders cannot get rid of ammonia from the body, so it can reach high levels, leading to serious problems including disability, brain damage and death. The active substance in Ammonaps, sodium phenylbutyrate, is converted into a substance called phenylacetate in the body. Phenylacetate combines with the amino acid glutamine, which contains nitrogen, to form a substance that can be removed from the body by the kidneys. This allows the levels of nitrogen in the body to decrease, reducing the amount of ammonia produced.

How has it been studied?

Ammonaps has been studied in 82 patients with urea cycle disorders who were treated with Ammonaps and had not received other treatments for their disease before. Ammonaps was not compared with any other treatments. The main measure of effectiveness was survival, but the study also looked at the number of hyperammonaemic episodes (periods of very high blood ammonia levels), cognitive development (development of the ability to think, learn and remember), growth, and blood ammonia and glutamine levels.

What benefits has it shown during the studies?

The overall survival rate was about 80% in newborn babies who received Ammonaps. In contrast, untreated newborns usually die within the first year of life. The survival rate was higher in patients who had developed the disease later in life. Early diagnosis and immediate treatment are important to reduce the risk of disability.

What is the risk associated?

The most common side effects with Ammonaps (seen in more than 1 patient in 10) are amenorrhoea (absence of periods) and irregular menstruation (irregular periods), but these only occur in fertile female patients. Other common side effects include abnormal kidney function and blood cell counts (red cells, white cells and platelets). For the full list of all side effects reported with Ammonaps, see the Package Leaflet.
Ammonaps should not be used in people who may be hypersensitive (allergic) to sodium phenylbutyrate or any of the other ingredients. It must not be used in patients who are pregnant or breast-feeding.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that urea cycle disorders are a serious disease with few treatments available, and that Ammonaps has been shown to prevent ammonia levels becoming too high. Therefore, despite the limited information available, the CHMP decided that Ammonaps’s benefits are greater than its risks as adjunctive therapy in the chronic management of urea cycle disorders. The Committee recommended that Ammonaps be given marketing authorisation.
Ammonaps was authorised under ‘Exceptional Circumstances’, because, as the disease is rare, limited information was available at the time of approval. As the company had supplied the additional information requested, the ‘Exceptional Circumstances’ ended on 6 July 2004.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Ammonaps on 8 December 1999. The marketing authorisation was renewed on 8 December 2004 and on 8 December 2009. The marketing authorisation holder is Swedish Orphan International AB.

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