Trade Names:Ammonul- Injection sodium benzoate 100 mg/sodium phenylacetate 100 mg
Sodium phenylacetate and sodium benzoate are metabolically active compounds that can serve as alternatives to urea for the excretion of waste nitrogen. Phenylacetate conjugates with glutamine in the liver to form phenylacetylglutamine (renally excreted), and benzoate conjugates with glycine to form hippuric acid (renally excreted). This results in reduction of waste nitrogen levels in patients with deficiencies of urea cycle enzymes, thus attenuating ammonia and glutamine-induced neurotoxicity.
Sodium phenylacetate and sodium benzoate follow nonlinear pharmacokinetics after IV infusion. Following a 90 min IV infusion of sodium phenylacetate, the AUC for doses of 1 and 5.5 g/m 2 were 175.6 and 3,829.2 mcg•h/mL, respectively. Following a 90 min IV infusion of sodium benzoate, the AUC for doses of 1 and 5.5 g/m 2 were 20.3 and 1,599.1 mcg•h/mL, respectively.
The total Cl for sodium phenylacetate decreased from 1.82 to 0.89 mcg•h/mL, with increasing doses of 3.75 and 4 g/m 2 , respectively. The total Cl for sodium benzoate decreased from 5.19 to 3.62 L/h/m 2 , with increasing doses of 3.75 and 5.5 g/m 2 , respectively.
For effective sodium phenylacetate and sodium benzoate therapy, renal Cl of the drug metabolites, and subsequently ammonia, is required. Closely monitor patients with impaired renal function.Hepatic Function Impairment
Limited data are available; however, because the liver is one of the organs in which the metabolic conjugation of sodium phenylacetate and sodium benzoate is known to occur, administer with care to patients with hepatic function impairment.Gender
Bioavailability of phenylacetate and benzoate was slightly higher in women than men; however, conclusion cannot be drawn because of the small number of subjects in the study.
Adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzyme of the urea cycle.
IV Loading and maintenance doses: 2.5 mL/kg of sodium phenylacetate and sodium benzoate, and 2 mL/kg of arginine 10% injection.Patients weighing at least 20 kg
IV Loading and maintenance doses: 55 mL/m 2 of sodium phenylacetate and sodium benzoate, and 2 mL/kg of arginine 10% injection.Arginosuccinate Synthetase (ASS) and Arginosuccinate Lyase (ASL) DeficienciesPatients weighing 0 to 20 kg
IV Loading and maintenance doses: 2.5 mL/kg of sodium phenylacetate and sodium benzoate, and 6 mL/kg of arginine 10% injection.Patients weighing at least 20 kg
IV Loading and maintenance doses: 55 mL/m 2 of sodium phenylacetate and sodium benzoate, and 6 mL/kg of arginine 10% injection.Patients Suspected of Having ASS Deficiency
IV Patients suspected of having ASS should be infused with sodium phenylacetate and sodium benzoate injection and 600 mg/kg of arginine as a loading dose over a 6-h infusion period. If patient is confirmed with ASS, then the loading dose infusion is administered over 90 min.
Store vials of injection concentrate at controlled room temperature (59° to 86°F). Diluted solutions are stable for up to 24 h at room temperature and room lighting conditions.
May compete with phenylacetylglutamine and hippurate for active renal tubular secretion.Probenecid
May compete with phenylacetylglutamine and hippurate for renal excretion.Valproic acid
May exacerbate urea cycle disorders and antagonize the efficacy of sodium phenylacetate/sodium benzoate.
None well documented.
Cardiac disorder (9%); vascular disorder (6%); hypotension (4%).
CNS disorders (22%); convulsions, mental impairment (6%); brain edema, psychiatric disorder, pyrexia (5%); agitation, coma (3%).
Skin and subcutaneous disorders (6%).
GI disorders (13%); vomiting (12%); diarrhea, nausea (3%).
Renal and urinary disorders (4%); UTI (3%).
Anemia (4%); disseminated intravascular coagulation (3%).
Metabolism and nutrition disorders (21%); hyperglycemia, hypokalemia (7%); hyperammonemia (5%); metabolic acidosis (4%); acidosis, hypocalcemia (3%).
Mediastinal, respiratory, and thoracic disorders (15%); respiratory distress (3%).
Administration-site conditions, general disorders (14%); infections (12%); injury, poisoning, procedural complications (4%); injection-site reactions (3%).
Monitor plasma ammonia levels, electrolytes, neurological status, and clinical response to treatment. Closely monitor infusion site for possible infiltration during infusion.
Category C .
Has been used in children, including patients in the early neonatal period.
Use with caution.
Use with caution.
Uncontrolled hyperammonemia can rapidly result in brain damage or death and should be treated as a life-threatening emergency, using all therapies necessary to reduce ammonia levels.
High-dose arginine administration may result in hyperchloremic acidosis. Monitor plasma chloride and bicarbonate levels; administer bicarbonate, as appropriate, to maintain acid-base balance.
Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein.
Once ammonia levels have been reduced to the normal range, start or reinitiate oral therapy such as sodium phenylbutyrate, dietary management, and protein restriction.
Extravasation may lead to skin necrosis. If extravasation occurs or is suspected, discontinue infusion and resume at a different infusion site. Treat extravasation by aspiration of residual drug from catheter, limb elevation, and intermittent cooling using cold packs.
May develop because urine potassium loss is enhanced during treatment; be prepared to treat appropriately.
Do not administer repeat loading doses because of prolonged phenylacetate plasma levels.
May cause nausea and vomiting. Consider using antiemetic during infusion.
Neurotoxicity (disorientation, exacerbation of preexisting neuropathy, fatigue, headaches, impaired memory, light-headedness, somnolence) was reported in cancer patients receiving IV phenylacetate (250 to 300 mg/kg/day for 14 days every 4 wk).
Because of structural similarities of phenylacetate and benzoate to salicylate, adverse reactions typically associated with salicylate overdose (eg, hyperventilation, metabolic acidosis) may develop. Monitor blood pH and pCO 2 frequently during infusion.
Contains sodium 30.5 mg/mL of undiluted product. Use with caution, if at all, in patients with heart failure, severe renal function impairment, or clinical states with sodium retention and edema.
Obtundation, hyperventilation, severe compensated metabolic acidosis, large anion gap, hypernatremia, hyperosmolarity, progressive encephalopathy, CV collapse, death caused by cardiorespiratory failure, hyperammonemia, increased intracranial pressure, pneumonitis with septic shock and coagulopathy, respiratory failure, intractable hypotension, and probable sepsis.
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