AMMONUL Neonatal

MEDICATION	DOSAGES & INTERVALS OF ADMINISTRATION	ROUTE & FINAL DILUTION	DILUTION INSTRUCTIONS	STABILITY	RATE OF INFUSION & COMMENTS
AMMONUL (Neo) (Sodium phenylacetate 10% and Sodium Benzoate 10%) Mechanism of action: Alternative pathway for waste nitrogen excretion reducing the risk for ammonia and glutamine induced neurotoxicity. Phenylacetate is conjugated with glutamine by acetylation to form phenylacetylglutamine. Phenylacetylglutamine is excreted renally and results in the removal of 2 moles of nitrogen for each mole of phenylacetate administered. Benzoate is conjugated with glycine to form hippurate. Hippurate is excreted renally and results in removal of 1 mole of nitrogen for each mole of benzoate administered. 50 mL vial (sodium phenylacetate 10% and sodium benzoate 10%) Each mL contains: 100 mg sodium phenylacetate and 100 mg of sodium benzoate. Product contains 30.5 mg/mL of sodium (1.3 mmol/mL). Ref: Last update: 2023-08-01	Adjunctive Treatment of Acute Hyperammonemia in Neonates with Urea Cycle Disorders For Infants with no diagnosed defect or any defect in Urea cycle: Loading Dose(Priming Solution):2.5 mL/kg of Ammonul in combination with10% arginine HCl 250 to 400mg/kg and KCl 0.25 mmol/Kg diluted in 25 to 35mL/kg of Dextrose 10% given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart. Maintenance Dose(Sustaining Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 250 to 400mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35 mL/Kg of Dextrose 10%given as an IV infusion over 24 hours. NAGS, CPS or OTC Deficiency: Loading Dose(Priming Solution): 2.5mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCl 0.25 mmol/kg diluted in 25 to 35mL/kg of Dextrose 10% given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart. Maintenance Dose(Sustaining Solution): 2.5mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35mL/kg of Dextrose 10%given as an IV infusion over 24 hours. ASS Deficiency: Loading Dose(Priming Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCL 0.25 mmol/kg diluted in 25 to 35mL/kg of Dextrose 10%given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart. Maintenance Dose(Sustaining Solution): 2.5mL/kg of Ammonul in combination with 10% arginineHCl 250mg/kg and KCL 2 mmol/100 mL diluted in 25 to 35mL/kg of Dextrose 10% as an IV infusion over 24 hours. ASL Deficiency: Loading Dose(Priming Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 200 to 400 mg/kg and KCl 0.25 mmol/kg diluted in 25-35 mL/kg of Dextrose 10% as an IV infusion over 120 minutes. Maintenance Dose(Sustaining Solution): 2.5 mL/kg Ammonul in combination with 10% arginine HCl 200 to 400 mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35 mLkg of Dextrose 10% as an IV infusion over 24 hours. Do not exceed 5 mL/kg/day of Ammonul NAGS = N-acetylglutamate Synthase CPS = carbamyl phosphate synthetase OTC = ornithine transcarbamylase ASS = argininosuccinic acid synthetase ASL = argininosuccinic acid lyase	IV	Supplied by Pharmacy.	24 hours Room Temperature	Administration: See Dosages Section. COMMENTS: Administration: Arginine HCL is mixed together with Ammonul in the same dextrose solution. Must be administered via central venous line because extravasation may cause irritation, burns and tissue necrosis. If central venous access is not readily available may be give through a peripheral venous line on a limited basis with close monitoring of IV site until central venous access can be obtained. Adverse Effects: vomiting, hyperglycemia, hypokalemia, hypotension. Monitoring: -Monitor ammonia levels until levels remain less than 200 to 300 micromoles/L. -Monitor blood glucose, electrolytes, and acid base status. An anion gap > 15 mmol/L or which has increased by > 6 mmol/L from baseline may indicate drug accumulation. -Monitor amino acids to assess effectiveness of citrulline/arginine replacement and glutamine removal. -Monitor liver transaminases (AST, ALT). Standard Prescription: Ammonul__mL (__mL/kg) in combination with arginine HCL IV x 1 loading dose Ammonul__mL in combination with arginine HCL IV infusion over __hours

MEDICATION

DOSAGES & INTERVALS OF ADMINISTRATION

ROUTE & FINAL DILUTION

DILUTION INSTRUCTIONS

STABILITY

RATE OF INFUSION & COMMENTS

AMMONUL (Neo)
(Sodium phenylacetate 10% and Sodium Benzoate 10%)

Mechanism of action:

Alternative pathway for waste nitrogen excretion reducing the risk for ammonia and glutamine induced neurotoxicity. Phenylacetate is conjugated with glutamine by acetylation to form phenylacetylglutamine. Phenylacetylglutamine is excreted renally and results in the removal of 2 moles of nitrogen for each mole of phenylacetate administered. Benzoate is conjugated with glycine to form hippurate. Hippurate is excreted renally and results in removal of 1 mole of nitrogen for each mole of benzoate administered.

50 mL vial

(sodium phenylacetate 10% and sodium benzoate 10%)

Each mL contains:

100 mg sodium phenylacetate and 100 mg of sodium benzoate.

Product contains 30.5 mg/mL of sodium (1.3 mmol/mL).

Ref:

Last update: 2023-08-01

Adjunctive Treatment of Acute Hyperammonemia in Neonates with Urea Cycle Disorders

For Infants with no diagnosed defect or any defect in Urea cycle:

Loading Dose(Priming Solution):2.5 mL/kg of Ammonul in combination with10% arginine HCl 250 to 400mg/kg and KCl 0.25 mmol/Kg diluted in 25 to 35mL/kg of Dextrose 10% given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart.

Maintenance Dose(Sustaining Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 250 to 400mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35 mL/Kg of Dextrose 10%given as an IV infusion over 24 hours.

NAGS, CPS or OTC Deficiency:

Loading Dose(Priming Solution): 2.5mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCl 0.25 mmol/kg diluted in 25 to 35mL/kg of Dextrose 10% given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart.

Maintenance Dose(Sustaining Solution): 2.5mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35mL/kg of Dextrose 10%given as an IV infusion over 24 hours.

ASS Deficiency:

Loading Dose(Priming Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 250mg/kg and KCL 0.25 mmol/kg diluted in 25 to 35mL/kg of Dextrose 10%given as an IV infusion over 120 minutes. Reloading only in neonates with severe disorders or those undergoing dialysis. Doses should be spaced 6 hours apart.

Maintenance Dose(Sustaining Solution): 2.5mL/kg of Ammonul in combination with 10% arginineHCl 250mg/kg and KCL 2 mmol/100 mL diluted in 25 to 35mL/kg of Dextrose 10% as an IV infusion over 24 hours.

ASL Deficiency:

Loading Dose(Priming Solution): 2.5 mL/kg of Ammonul in combination with 10% arginine HCl 200 to 400 mg/kg and KCl 0.25 mmol/kg diluted in 25-35 mL/kg of Dextrose 10% as an IV infusion over 120 minutes.

Maintenance Dose(Sustaining Solution): 2.5 mL/kg Ammonul in combination with 10% arginine HCl 200 to 400 mg/kg and KCl 2 mmol/100 mL diluted in 25 to 35 mLkg of Dextrose 10% as an IV infusion over 24 hours.

Do not exceed 5 mL/kg/day of Ammonul

NAGS = N-acetylglutamate Synthase

CPS = carbamyl phosphate synthetase

OTC = ornithine transcarbamylase

ASS = argininosuccinic acid synthetase

ASL = argininosuccinic acid lyase

Supplied by Pharmacy.

24 hours

Room Temperature

Administration:
See Dosages Section.

COMMENTS:

Administration: Arginine HCL is mixed together with Ammonul in the same dextrose solution. Must be administered via central venous line because extravasation may cause irritation, burns and tissue necrosis. If central venous access is not readily available may be give through a peripheral venous line on a limited basis with close monitoring of IV site until central venous access can be obtained.

Adverse Effects: vomiting, hyperglycemia, hypokalemia, hypotension.

Monitoring:

-Monitor ammonia levels until levels remain less than 200 to 300 micromoles/L.

-Monitor blood glucose, electrolytes, and acid base status. An anion gap > 15 mmol/L or which has increased by > 6 mmol/L from baseline may indicate drug accumulation.

-Monitor amino acids to assess effectiveness of citrulline/arginine replacement and glutamine removal.

-Monitor liver transaminases (AST, ALT).

Standard Prescription:

Ammonul__mL (__mL/kg) in combination with arginine HCL IV x 1 loading dose

Ammonul__mL in combination with arginine HCL IV infusion over __hours