EFFICACY4,5

The efficacy of AMMONUL (sodium phenylacetate and sodium benzoate) Injection 10%/10% in improving patient survival at the end of an acute hyperammonemic episode was demonstrated in an uncontrolled open-label study in which 316 patients received the drug during a combined 1045 episodes of hospitalization. The study took place between 1981 and 2003 in the United States.

AMMONUL rapidly reduces elevated ammonia levels

  • Within four hours of initiation of AMMONUL therapy, mean ammonia levels decreased significantly and were maintained in patients responding to therapy.
    • How rapidly nitrogen is removed depends on the level of enzyme activity responsible for formation of hippurate and phenylacetylglutamine, which may vary by individual.
  • AMMONUL effectively reduces ammonia levels caused by the following enzyme deficiencies: carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinic acid synthetase (ASS), and argininosuccinic acid lyase (ASL).
  • In 91% of episodes, ammonia levels decreased from very high (>4x upper limit of normal [ULN]) to lower levels after treatment. In 4% of episodes, levels shifted from high (≤4x ULN) to very high (>4x ULN).
    • Dialysis is recommended for those patients who fail to have a significant reduction in plasma ammonia levels within 4 to 8 hours after receiving AMMONUL.
  • The mean (SD) duration of treatment was 4.6 (6.45) days per episode (range 1 to 72 days).
  • The percentage of neo-natal clinical trial patients who needed dialysis after 8 hours of AMMONUL treatment was low (13% of episodes).
  • 94% of all episodes (981 of 1045) were survived. Some patients in the clinical trial survived multiple episodes.
  • 80% of patients (252 of 316) survived their last episode.
  • Patient survival rates for male and female OTC patients were 72% and 89% respectively at last known episode, while episode survival rates for male and females OTC patients were 91% and 98%.5

AMMONUL improves or maintains neurologic status

  • Neurological status was improved or maintained in 93% of all episodes after treatment versus before treatment.
  • Recovery from coma was observed in 97% of episodes where coma was present at admission (111 of 114 episodes).

Important Safety Information for AMMONUL Injection 10% / 10%

  • IMPORTANT: Filtration required. Due to the possibility that particulate matter may impact the safe use of this product and to ensure optimal patient care, you are instructed to use the Millex® Durapore GV 33 mm Sterile Syringe Filter (0.22 μm) during the admixture process when injecting AMMONUL into the 10% dextrose IV bag. Note that particulate matter may not be readily seen on visual inspection, so this filter must be employed in all cases regardless of whether particulate matter is seen in the vial.
  • The most common adverse reactions are vomiting (9%), hyperglycemia (7%), hypokalemia (7%), convulsions (6%), and mental impairment (6%).
  • Dilute AMMONUL with sterile 10% Dextrose Injection (D10W) before administration. Use a central venous catheter line; use of a peripheral line may cause burns.
  • Monitor patients for prolonged exposure to elevated plasma ammonia levels as this can rapidly result in injury to the brain or death. Promptly use any therapies necessary to reduce plasma ammonia levels.
  • Monitor plasma potassium levels carefully and treat as necessary.
  • Use caution if AMMONUL is administered to patients with congestive heart failure, severe renal insufficiency, or with a condition in which there is sodium retention with edema.
  • Monitor the infusion site for possible tissue infiltration since extravasation of AMMONUL into the perivenous tissues during high flow bolus infusion may lead to skin necrosis, especially in infants.
  • Do not administer repeat loading doses because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies.
  • Monitor patient blood chemistry profiles and perform frequent blood pH and pCO2 measurements because AMMONUL may cause side effects typically associated with salicyclate overdose such as hyperventilation and metabolic acidosis.
  • Administration of valproic acid to patients with urea cycle disorders may exacerbate their condition and antagonize the efficacy of AMMONUL.

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