Sodium Phenylacetate and Sodium Benzoate

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Sodium Phenylacetate and Sodium Benzoate provides an alternate vehicle to urea for waste nitrogen excretion in patients with urea cycle disorders. Urea cycle disorders may be caused by mutations in the genes NAGS, CPS1, OTC, ASS1, ASL and ARG1.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Sodium Phenylacetate and Sodium Benzoate.

Excerpt from the Sodium Phenylacetate and Sodium Benzoate (Ammonul) drug label:
"Urea cycle disorders can result from decreased activity of any of the following enzymes: N-acetylglutamate synthetase (NAGS), carbamyl phosphate synthetase (CPS), argininosuccinate synthetase (ASS), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL), or arginase (ARG). The most frequently observed initial presenting symptoms in neonates include lethargy, seizures, poor feeding, neurologic changes, edema, and respiratory distress. Patients with milder forms of enzyme deficiencies may not present until late childhood, adolescence, or adulthood. Hyperammonemic crisis with lethargy, delirium, and coma, in these patients, are often precipitated by viral illness, high protein diet, stress, or trauma."

"Plasma and urine amino acid analyses are used to diagnose ASS and ASL and to provide a preliminary diagnosis of CPS, OTC, or ARG. Blood citrulline levels are very low or absent in OTC and CPS, very high in ASS, and normal to moderately high in ASL and ARG. ASL may be distinguished by the presence of high levels of the unusual amino acid argininosuccinic acid (ASA) in the urine. It should be noted, however, that ASA tends to co-elute initially with other amino acids (such as leucine and isoleucine) in chromatographs, and may be missed on initial examination. ARG is characterized by high urine levels of arginine. A definitive diagnosis of CPS and OTC require a liver biopsy, and red blood cell enzyme analysis is needed to confirm a diagnosis of ARG. Patients suspected of having a urea cycle disorder, based on family history, should have documented hyperammonemia prior to administration of AMMONUL."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Sodium Phenylacetate and Sodium Benzoate (Ammonul) drug label PDF.