AMMONUL^®
(sodium phenylacetate and/sodium benzoate) Injection
10% / 10%

FAQs

• Single use glass vial that contains 50 mL of sodium phenylacetate and sodium benzoate 10%/10%.
• Each mL of AMMONUL contains 100 mg of sodium phenylacetate and 100 mg of sodium benzoate and water for injection.
• AMMONUL is available as an injection for intravenous administration via a central line only after dilution with sterile Dextrose Injection, 10%.
• AMMONUL contains 30.5 mg of sodium per mL of undiluted product. AMMONUL should be used with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema.

• AMMONUL is indicated as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle.
• In acute neonatal hyperammonemic coma, in moderate to severe episodes of hyperammonemic encephalopathy, and in episodes of hyperammonemia, which fail to respond to an initial course of AMMONUL therapy, hemodialysis is the most rapid and effective technique for removing ammonia. In such cases, the concomitant administration of AMMONUL can help prevent the re-accumulation of ammonia by increasing waste nitrogen excretion.
• Sodium phenylacetate and sodium benzoate are metabolically active compounds that serve as alternatives to urea for the excretion of waste nitrogen.

• Intravenous use of AMMONUL is complementary with the use of dialysis. In the non-neonatal study patient population treated with AMMONUL, dialysis (standard hemodialysis, peritoneal dialysis, arteriovenous hemofiltration, or other dialysis) was required in 13% of hyperammonemic episodes. Standard hemodialysis was the most frequently used dialysis method. High levels of ammonia can be reduced quickly when AMMONUL is used with dialysis, as the ammonia-scavenging of AMMONUL suppresses the production of ammonia from catabolism of endogenous protein and dialysis eliminates the ammonia and ammonia conjugates.
• Hyperammonemic coma (regardless of the cause) in the newborn infant should be aggressively treated. All patients should be promptly hemodialyzed as the procedure of choice using the largest catheters consistent with the patient’s size.
• Clearance of ammonia is approximately ten times greater by hemodialysis than by peritoneal dialysis or hemofiltration.
• Hemodialysis may be repeated until plasma ammonia level is stable at normal or near normal levels.

• IMPORTANT: Filtration now 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 GV33 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.
• AMMONUL must be administered intravenously through a central line. Administration through a peripheral line may cause burns.
• AMMONUL must be diluted with sterile Dextrose Injection, 10% (D10W) before administration. Dilution and dosage of AMMONUL is determined by weight for neonates, infants and young children and body surface area for larger patients, including older children, adolescents and adults (See Table 3 in the AMMONUL prescribing information).
• AMMONUL infusion should be started as soon as the diagnosis of hyperammonemia is made.
• AMMONUL is administered as a loading dose infusion administered over 90 to 120 minutes, followed by an equivalent maintenance dose infusion administered over 24 hours.
• AMMONUL may not be administered by any route other than intravenously through a central line. Analogous drugs, such as BUPHENYL (sodium phenylbutyrate) Tablets or Powder should be terminated prior to AMMONUL infusion.
• AMMMONUL should be administered in conjunction with caloric supplementation. Non-protein calories should be supplied principally as glucose (8-10 mg/kg/min) with Intralipid^® added. Attempts should be made to maintain a caloric intake of greater than 80 cal/kg/d.
• Because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies, repeat loading doses of AMMONUL should not be administered.

• The shelf life of AMMONUL is 36 months from the date of manufacturing.
• AMMONUL solutions are physically and chemically stable for up to 24 hours at room temperature and room lighting conditions. No compatibility information is presently available for AMMONUL infusion solutions except for Arginine HCl Injection, 10%, which may be mixed in the same container as AMMONUL.

• AMMONUL must be diluted with sterile Dextrose Injection, 10% (D10W) before administration.
• No compatibility information is presently available for AMMONUL infusion solution except for Arginine HCl Injection, 10%, which may be mixed in the same container as AMMONUL.
• Other infusion solutions and drug products should not be administered together with AMMONUL infusion solution.

• Intravenous arginine is an essential component of therapy for patients with carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or argininosuccinate lyase (ASL) deficiency. Plasma levels of chloride and bicarbonate should be monitored and appropriate amounts of bicarbonate administered.
• Pending a specific diagnosis, intravenous arginine (6 mL/kg of Arginine HCl Injection, 10%, over 90 minutes followed by the same dose over 24 hours) should be given to hyperammonemic infants suspected of having a UCD for two reasons: 1) infants with deficiencies in enzymes of the urea cycle (apart from arginase deficiency) are usually arginine-deficient; 2) hyperammonemia in infants with ASS or ASL deficiency usually respond favorable to arginine administration.
• If deficiencies of ASS or ASL are excluded as diagnostic possibilities, the intravenous dose of arginine should be reduced to 2 mL/kg/d Arginine HCl Injection, 10%.

• The most frequently reported adverse events were vomiting (9% of patients), hyperglycemia (7% of patients), hypokalemia (7% of patients), convulsions (6% of patients), and mental impairment (6% of patients).
• AMMONUL infusion has been associated with nausea and vomiting. An antiemetic may be administered during AMMONUL infusion.
• Adverse events leading to study drug discontinuation occurred in 4% of patients.

• 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 excretion 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.

• In case of an 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.)

• No, BUPHENYL and AMMONUL are not the same products and should not be substituted for each other. BUPHENYL is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). AMMONUL is indicated to treat acute hyperammonemia, which is a life-threatening emergency. Click here for more information on BUPHENYL.

• AMMONUL should be stored at 25ºC (77ºF), excursions permitted to 15º–30ºC (59º–86ºF).

• AMMONUL is available by prescription only.
• In the United States, AMMONUL may be ordered through ASD Healthcare at 888-AMMONUL (888-266-6685). If you are located outside of the U.S. please call Ucyclyd at 888-829-2593.
• Any questions or concerns you may have regarding AMMONUL should be directed to Ucyclyd at 888-829-2593.

• To report an adverse event, please call PROSAR at the following numbers:
  United States: 1.800.900.6389
  Canada: 1.800.420.8941
  International: 1.651.632.6781