Formal drug interaction studies have not been performed with AMMONUL.
Some antibiotics such as penicillin may compete with phenylacetylglutamine and hippurate for active secretion by renal tubules, which may affect the overall disposition of the infused drug.
Probenecid is known to inhibit the renal transport of many organic compounds, including aminohippuric acid, and may affect renal excretion of phenylacetylglutamine and hippurate.
There have been reports that valproic acid can induce hyperammonemia through inhibition of the synthesis of N-acetylglutamate, a co-factor for carbamyl phosphate synthetase. Therefore, administration of valproic acid to patients with urea cycle disorders may exacerbate their condition and antagonize the efficacy of AMMONUL.
Use of corticosteroids may cause a protein catabolic state and, thereby, potentially increase plasma ammonia levels in patients with impaired ability to form urea.
Overdosage has been reported during AMMONUL treatment in urea cycle-deficient patients. All patients in the uncontrolled open-label study were to be treated with the same dose of AMMONUL. 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 AMMONUL. 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 AMMONUL, 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).