AMMONAPS 500MG Tablet

Pharmacotherapeutic group: products for the treatment of various disorders of the digestive tract and metabolism, ATC code: A16AX03. Sodium phenylbutyrate is a prodrug and is rapidly metabolised to phenylacetate.‍​‍‍‍​‍‍‍‍‍‍‍‍​‍ Phenylacetate is the metabolically active compound, which conjugates with glutamine by acetylation to form phenylacetylglutamine, which is excreted by the kidneys. On a molar basis, phenylacetylglutamine is comparable to urea (each contains 2 moles of nitrogen), thus providing an alternative vehicle for waste nitrogen excretion. Based on studies measuring urinary phenylacetylglutamine excretion in patients with urea cycle disorders, it is estimated that for each gram of sodium phenylbutyrate administered, between 0.12 and 0.15 g of phenylacetylglutamine is produced. As a result, sodium phenylbutyrate lowers elevated plasma levels of ammonia and glutamine in patients with urea cycle disorders. It is important to establish the diagnosis early and to initiate treatment immediately in order to improve survival and clinical outcome. Previously, the neonatal-onset form of urea cycle disorder was almost always fatal during the first year of life, even when treated with peritoneal dialysis and essential amino acids or their nitrogen-free analogues. With haemodialysis, use of alternative metabolic pathways for waste nitrogen excretion (sodium phenylbutyrate, sodium benzoate and sodium phenylacetate), dietary protein restriction and, in some cases, supplementation with essential amino acids, survival increased to nearly 80% in neonates diagnosed after birth (but within the first month of life), with the majority of deaths occurring during episodes of acute hyperammonaemic encephalopathy. A high incidence of intellectual disability was observed in patients with the neonatal-onset form of the disease. In patients diagnosed during pregnancy and treated before the occurrence of a hyperammonaemic encephalopathy episode, survival was 100%, but even in these patients, many subsequent cognitive impairments and neurological deficits occurred. In patients with late-onset deficiency, including women with the heterozygous form of ornithine transcarbamylase deficiency, who survived hyperammonaemic encephalopathy and were treated long-term with dietary protein restriction and sodium phenylbutyrate, survival was 98%. The majority of patients had IQ test results averaging in the low average/borderline intellectual disability range. Their cognitive performance remained relatively stable during phenylbutyrate treatment. Exacerbation of existing neurological impairment is unlikely during treatment, and in some patients neurological impairment may persist. It is possible that AMMONAPS will need to be taken for life unless orthotopic liver transplantation is performed.