Ammonaps
Authorised
This medicine is authorised for use in the European Union
sodium phenylbutyrate
MedicineHumanAuthorised
- Application under evaluation
- CHMP opinion
- European Commission decision
Overview
This is a summary of the European Public Assessment Report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).
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).
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.
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.
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.
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.
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.
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.
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.
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.
Product information
Latest procedure affecting product information:
IAIN/0063
12/12/2022
This medicine’s product information is available in all official EU languages.
Select 'available languages' to access the language you need.
Product information documents contain:
- summary of product characteristics (annex I);
- manufacturing authorisation holder responsible for batch release (annex IIA);
- conditions of the marketing authorisation (annex IIB);
- labelling (annex IIIA);
- package leaflet (annex IIIB).
Product details
- Name of medicine
- Ammonaps
- Active substance
- Sodium phenylbutyrate
- International non-proprietary name (INN) or common name
- sodium phenylbutyrate
- Therapeutic area (MeSH)
- Ornithine Carbamoyltransferase Deficiency Disease
- Citrullinemia
- Carbamoyl-Phosphate Synthase I Deficiency Disease
- Anatomical therapeutic chemical (ATC) code
- A16AX03
Pharmacotherapeutic group
Other alimentary tract and metabolism productsTherapeutic indication
Ammonaps is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or
argininosuccinate synthetase.
It is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease
(partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.
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