What is Ammonaps?
Ammonaps is a medicine that contains sodium phenylbutyrate as the active ingredient, available in
form of white oval tablets (500 mg) or granules (940 mg / g).
What is Ammonaps used for?
Ammonaps is used to treat patients with urea cycle disorders. In these patients, the body is unable to expel nitrogen residues as it lacks certain enzymes usually contained in the liver. In the body, nitrogenous residues are present in the form of ammonia, a substance particularly toxic to the brain. Ammonaps is indicated for patients with a deficiency of one or more of the following enzymes: carbamylphosphate synthetase, ornithine transcarbamylase or arginosuccinic synthetase.
The medicine can be administered to patients in whom the disorder has the following characteristics:
• early neonatal onset (total lack of one or more of the aforementioned enzymes that occurs in the first month of life);
• late onset (partial enzyme deficiency that occurs after the first month of life) in subjects who have suffered brain damage caused by a high rate of ammonia.
The medicine can only be obtained with a prescription.
How is Ammonaps used?
Treatment with Ammonaps should be followed by a doctor experienced in treating patients with urea cycle disorders.
Ammonaps is used in addition to other treatments, along with a special low-protein dietary regime aimed at reducing nitrogen intake. The daily dose of Ammonaps varies according to the patients and according to the diet followed, body weight and height. Regular blood tests are therefore necessary to determine the exact daily dose. The daily dose of Ammonaps must be evenly distributed between meals. The tablets are for adults and children, while the granules are for newborns and for patients who are unable to swallow the tablets. The granules are mixed with food or a drink, immediately before intake, or dissolved in water before being administered by probe from the abdomen or from the nose to the stomach.
Ammonaps is a long-term treatment, until the patient successfully undergoes a liver transplant operation.
How does Ammonaps work?
Nitrogen is introduced into the body through the proteins contained in the food, then transformed into ammonia. In patients with urea cycle disorders the body is not able to eliminate the ammonia present in the body, which then accumulates inside it. This accumulation causes serious repercussions such as disability, brain damage and death. The active substance in Ammonaps, sodium phenylbutyrate, is transformed by the body into a substance called phenylacetate. Phenylacetate combines with glutamine, an amino acid that contains nitrogen, to form a substance that can be eliminated from the body by the kidneys. This reduces nitrogen accumulation, thus reducing the amount of ammonia produced by the body.
How has Ammonaps been studied?
The medicine was studied in 82 patients suffering from urea cycle disorders who were treated with Ammonaps and who had not previously received other treatments for the said disorder. Ammonaps was not compared to any other treatment. The main efficacy index was survival, although the study also considered the number of episodes of hyperammonemia (intervals characterized by very high levels of ammonia in the blood), cognitive development (ie the development of the ability to think, to learn and remember), the growth and levels of ammonia and glutamine in the blood.
What benefit has Ammonaps shown during the studies?
The overall survival rate was approximately 80% in newborns treated with Ammonaps. On the other hand, untreated infants usually die within the first year of life. In patients who developed the disease at a later date the recorded survival rate was higher. Early diagnosis and immediate treatment are important to reduce the risk of disability.
What is the risk associated with Ammonaps?
The most common side effects with Ammonaps (seen in more than 1 patient in 10) are amenorrhea (absence of a menstrual cycle) or irregular menstrual cycles, although this only applies to female patients of childbearing age. Other common side effects include impaired renal function and blood cell count abnormalities (red blood cells, white blood 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. The medicine should not be administered during pregnancy or breastfeeding.
Why has Ammonaps been approved?
The Committee for Medicinal Products for Human Use (CHMP) found that disorders of the urea cycle constitute a serious disease for which there is a reduced number of treatments.
Ammonaps has been shown to prevent excessive accumulation of ammonia in the blood. Despite the limited information available, the CHMP decided that the benefits of Ammonaps outweigh the risks as an adjunctive therapy in the chronic treatment of urea cycle disorders and therefore recommended that it be given marketing authorization.
Ammonaps had been authorized in "exceptional circumstances", since limited information was available at the time of approval for treatment of a rare disease. Since the company provided the additional information requested, the "in exceptional circumstances" restriction was removed on 6 July 2004.
More information on Ammonaps:
On 8 December 1999 the European Commission issued a marketing authorization for Ammonaps, valid throughout the European Union. The marketing authorization was renewed on 8 December 2004 and 8 December 2009. Marketing authorization holder is Swedish Orphan International AB. The full EPAR for Ammonaps can be found here.
Last update of this summary: 12-2009
