Table 4.

Medications used in acute management of hyperammonemia and their dosages

Medications	Mechanism of action	Dosage	Route	Adverse reaction*
Sodium benzoatea	Conjugation with glycine to form hippuric acid	Weight ≤20 kg: 250 mg/kg as loading dose over 90 minutes followed by 250–500 mg/kg/day Weight >20 kg: 5.5 g/m2 as loading dose over 90 minutes followed by 5.5 g/m2/dayb	IV	Cardiovascular: hypotension Dermatologic: injection site reaction Electrolytes imbalance: hyperglycemia, hypokalemia, hypernatremia Gastrointestinal: vomiting, diarrhea CNS: altered mental status, seizure, cerebral edema Other: fever
Sodium phenylacetatea	Conjugation with glutamine to form phenylacetylglutamine	Same as for Sodium benzoate	IV	Same as for Sodium benzoate
AMMONUL®c	Contains both sodium benzoate and sodium phenylacetate	Same as for Sodium benzoate	IV (AMMONUL® could be given through peripheral line on limited basis)	Same as for Sodium benzoate
L-Arginine	As an intermediate metabolite in the urea cycle. It can improve the flow through the urea cycle and thereby improves ammonia removal	250–400 mg/kg/day as loading dose over 90 minutes followed by 250–400 mg/kg/day	IV	Hyperchloremic metabolic alkalosis, hypokalemia, elevated BUN and creatinine levels, flushing, nausea, vomiting, abdominal cramps, bloating, numbness, headache
Carbaglu® (carglumic acid)d	Replace N-acetylglutamate as an activator of mitochondrial carbamoyl phosphate synthetase, the first enzyme of the urea cycle	100 mg/kg bolus per NG tube, then 25–62.5 mg/kg every 6 hours	NG	Abdominal pain, diarrhea, vomiting, anemia, otitis media, tonsillitis, nasopharyngitis, fever, headache

Notes:

^aIt should be given through central line, however, could be given peripherally on limited basis.

^bIf on hemodialysis/hemodiafiltration, maintenance doses should be increased to 350 mg/kg/day (or proportional increase for body surface-based dose calculation).

^cIt is supplied as a vial of 50 mL or 5,000 mg constituted of concentrated, aqueous 10% sodium benzoate and 10% sodium phenylacetate solution. Thus, each mL provides 100 mg of sodium benzoate and 100 mg of sodium phenylacetate in water. According to the prescribing information, AMMONUL must be diluted with sterile dextrose injection, 10% at ≥25 mL/kg before administration.

^dIt is supplied as 200 mg tablet; 5 or 60 tablets in a polypropylene bottle with polyethylene cap and desiccant unit.

^*Generally all the drugs are well tolerated and adverse reactions are only relevant if dosages are very high.

Abbreviations: BUN, blood urea nitrogen; IV, intravenous; NG, nasogastric; CNS, central nervous system.