Sodium Benzoate (3 brand names, 1 dosage form, 2 routes)
Available dosage forms: SOLUTION.
Routes of administration: ORAL, INTRAVENOUS.
Brand Names
- AMMONUL
- SODIUM PHENYLACETATE AND SODIUM BENZOATE
- UCEPHAN
Related Health Topics
Mechanism of Action
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). Sodium phenylacetate and sodium benzoate are metabolically active compounds that can serve as alternatives to urea for the excretion of waste nitrogen. Figure 2 is a schematic illustrating how the components of Sodium Phenylacetate and Sodium Benzoate Injection, phenylacetate and benzoate, provide an alternative pathway for nitrogen disposal in patients without a fully functioning urea cycle. Phenylacetate conjugates with glutamine in the liver and kidneys to form phenylacetylglutamine, via acetylation. Phenylacetylglutamine is excreted by the kidneys via glomerular filtration and tubular secretion. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (both contain two moles of nitrogen). Two moles of nitrogen are removed per mole of phenylacetate when it is conjugated with glutamine. Similarly, preceded by acylation, benzoate conjugates with glycine to form hippuric acid, which is rapidly excreted by the kidneys by glomerular filtration and tubular secretion. One mole of hippuric acid contains one mole of waste nitrogen. Thus, one mole of nitrogen is removed per mole of benzoate when it is conjugated with glycine. Figure 2 CPS = carbamyl phosphate synthetase; OTC = ornithine transcarbamylase; ASS = argininosuccinate synthetase; ASL = argininosuccinate lyase; ARG = arginase; NAGS = N-acetylglutamate synthetase
Overdosage
Overdosage has been reported during Sodium Phenylacetate and Sodium Benzoate Injection treatment in urea cycle-deficient patients. All patients in the uncontrolled open-label study were to be treated with the same dose of Sodium Phenylacetate and Sodium Benzoate Injection. However, some patients received more than the dose level specified in the protocol. In 16 of the 64 deaths, the patient received a known overdose of Sodium Phenylacetate and Sodium Benzoate Injection. Causes of death in these patients included cardiorespiratory failure/arrest (6 patients), hyperammonemia (3 patients), increased intracranial pressure (2 patients), pneumonitis with septic shock and coagulopathy (1 patient), error in dialysis procedure (1 patient), respiratory failure (1 patient), intractable hypotension and probable sepsis (1 patient), and unknown (1 patient). Additionally, other signs of intoxication may include obtundation (in the absence of hyperammonemia), hyperventilation, a severe compensated metabolic acidosis, perhaps with a respiratory component, large anion gap, hypernatremia and hyperosmolarity, progressive encephalopathy, cardiovascular collapse, and death. In case of overdose of Sodium Phenylacetate and Sodium Benzoate Injection, discontinue the drug and institute appropriate emergency medical monitoring and procedures. In severe cases, the latter may include hemodialysis (procedure of choice) or peritoneal dialysis (when hemodialysis is unavailable).