Ammonul (sodium benzoate/sodium phenylacetate)
Urea Cycle Disorder Agents Intravenous Vial (ML)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Sodium phenylacetate and sodium benzoate is a fixed combination of 2 ammonia detoxicants.
Sodium phenylacetate and sodium benzoate, a fixed combination of the 2 ammonia detoxicants, is used as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients with disorders (i.e, deficiencies in enzymes) of the urea cycle.
The urea cycle (which resides exclusively in periportal hepatocytes) is an essential biochemical pathway for waste nitrogen excretion. Toxic ammonia is converted by metabolic transformation to nontoxic water soluble urea and, as such, is eliminated in the urine. Because there is no effective secondary pathway for clearance of ammonia, disruption of the main pathway (associated with decreased activity of the enzymes the CPS (carbamyl phosphate synthetase), OTC (ornithine transcarbamylase), ASS (argininosuccinate synthetase), ASL (argininosuccinate synthetase lyase), ARG (arginase), and NAGS (N-acetylglutamate synthetase)) may result in accumulation of precursor metabolites (e.g., ammonia) in the urea cycle.
The rapid accumulation of ammonia and other precursor metabolites results in acute cerebral edema with severe neurologic compromise. Thus, fast and effective treatment (usually, dialysis and pharmacologic therapy) is essential for a satisfactory clinical outcome.
Sodium phenylacetate and sodium benzoate decrease ammonia concentrations by serving as alternatives to urea for the excretion of waste nitrogen. Phenylacetate is conjugated with glutamine in the liver and kidneys to form phenylacetylglutamine, and benzoate is conjugated with glycine to form hippuric acid; phenylacetylglutamine and hippuric acid subsequently are excreted in urine. Conjugation of 1 mole of phenylacetate with glutamine removes 2 moles of nitrogen, while conjugation of 1 mole of benzoate with glycine removes 1 mole of nitrogen.
The nitrogen content of phenylacetylglutamine is identical to that of urea (i.e., both contain 2 moles of nitrogen).
Glutamine and glycine used in these reactions are replaced by synthesis, thereby reducing the nitrogen pool and attenuating the risk of ammonia- and glutamine-induced neurotoxicity in patients with deficiencies of urea cycle enzymes.
Overview(R) (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Generic name: sodium benzoate/sodium phenylacetate
Drug class: Urea Cycle Disorder Agents
Therapeutic class: Metabolic Modifiers
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ammonul
Indications
The following indications are listed for Ammonul:
- Arginase Deficiency
- Argininosuccinate Lyase Deficiency
- Carbamoyl Phosphate Synthetase Deficiency
- Citrullinemia
- Hyperammonemia
- Isovaleric Acidemia
- Ornithine Carbamoyltransferase Deficiency
Also known as: Abnormally Elevated Blood Ammonia, Ammonemia, Argininosuccinate Synthetase Deficiency, Argininosuccinic Acid Synthetase Deficiency, Argininosuccinic Aciduria, Arginosuccinic Aciduria, Asal Deficiency, Asl Deficiency, Caps Deficiency, Carbamoyl-Phosphate Synthetase Deficiency, Cps Deficiency, Hyperammonemia Due To Ornithine Transcarbamylase Deficiency, Hyperammonemic Syndrome, Hyperargininemia, Isovaleryl Coa Dehydrogenase Deficiency, Isovaleryl-Coenzyme A Dehydrogenase Deficiency, Ornithine Transcarbamoylase Deficiency, Ornithine Transcarbamylase Deficiency.
Dosing
No dosing information is available for this tab.
The manufacturer has notified health-care professionals that particulate matter was detected in sodium phenylacetate and sodium benzoate injections. The manufacturer states that because of the possibility that this particulate matter may affect the safe use of the injection and to ensure optimal patient care, health-care professionals are instructed to use a Millex(R) Durapore GV 33 mm sterile syringe filter (0.22 mcm) when diluting sodium phenylacetate and sodium benzoate injection concentrate with dextrose 10% injection. (See Dilution under Dosage and Administration: Administration.) The manufacturer states that since this particulate matter may not be readily observed on visual inspection, a filter (i.e., Durapore GV 33 mm sterile syringe filter) must be used always regardless of whether particulate matter is seen in the vial. It has been confirmed that this particulate matter is removed when the aforementioned filter is used. As a precautionary measure, the manufacturer will package Millex(R) Durapore GV 33 mm sterile syringe filters with all shipments of sodium phenylacetate and sodium benzoate injection. For further information, see Detection of Particulate Matter in Commercial Preparations under Warnings/Precautions: Warnings, in Cautions.
Commercially available sodium phenylacetate and sodium benzoate injection must be diluted prior to IV infusion. (See Dilution under Dosage and Administration: Admistration.) The drug is infused IV through a central venous line because administration through a peripheral line may cause burns. The drug should be administered only by the IV route.
Because administration of sodium phenylacetate and sodium benzoate has been associated with nausea and vomiting, an antiemetic may be administered during infusion.
Sodium phenylacetate and sodium benzoate therapy should be initiated as soon as the diagnosis of hyperammonemia is made. Analogous oral agents (e.g., sodium phenylbutyrate) should be discontinued before initiation of the sodium phenylacetate and sodium benzoate infusion. Oral therapy (e.g., with sodium phenylbutyrate), dietary management, and protein restriction should be started or resumed when ammonia concentrations have been reduced to the normal range.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Formal drug interaction studies have not been performed.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to sodium phenylacetate or sodium benzoate.
- Severe renal impairment
- Chronic heart failure
- Edema
- Metabolic acidosis
- Disease of liver
- Hyperglycemia
- Hypokalemia
- Kidney disease with reduction in glomerular filtration rate (GFr)
- Seizure disorder
Adverse reactions
Adverse effects occurring in 6% or more of patients receiving sodium phenylacetate and sodium benzoate include vomiting, hyperglycemia, hypokalemia, seizures, and mental impairment.
More Frequent
- Hypokalemia
- Seizure disorder
Less Frequent
- Anemia
- Disseminated intravascular coagulation
- Metabolic acidosis
Rare or Very Rare
- Bradycardia
- Cardiomyopathy
- Cholestasis
- Drug-induced hepatitis
- Drug-induced psychosis
- Extravasation injury
- Hemorrhage
- Hypertension
- Hypotension
- Pancytopenia
- Pericardial effusion
- Renal failure
- Thrombocytopenic disorder
More Frequent
- Altered mental status
- Hyperglycemia
- Infection
- Vomiting
Less Frequent
- Diarrhea
- Fever
- Injection site sequelae
- Nausea
Rare or Very Rare
- Alopecia
- Ataxia
- Blistering skin
- Chest pain
- Flushing
- Pruritus of skin
- Skin rash
- Thrombophlebitis
- Urinary retention
- Urticaria
Precautions
No enhanced messaging available.
Efficacy for treatment of hyperammonemia has been established in pediatric patients 0-16 years of age, including neonates 0-30 days of age and infants 31 days-2 years of age. Efficacy was based on analysis of data from a series of hospitalizations in which patients with hyperammonemia or a potential urea cycle disorder were treated with sodium phenylacetate and sodium benzoate, given in conjunction with arginine. (See Uses: Acute Hyperammonemia.)
Category C. (See Users Guide)
Not known whether sodium phenylacetate or sodium benzoate or their conjugated metabolites are distributed into milk. Caution is advised if the drug is administered in nursing women.
No enhanced messaging available.
ICD codes
| Code | Type | Description |
|---|---|---|
| Arginase deficiency | ||
| E72.21 | ICD10CM | Argininemia |
| Argininosuccinate lyase deficiency | ||
| E72.22 | ICD10CM | Arginosuccinic aciduria |
| Carbamoyl phosphate synthetase deficiency | ||
| E72.29 | ICD10CM | Other disorders of urea cycle metabolism |
| Citrullinemia | ||
| E72.23 | ICD10CM | Citrullinemia |
| Hyperammonemia | ||
| B15.0 | ICD10CM | Hepatitis A with hepatic coma |
| B16.0 | ICD10CM | Acute hepatitis B with delta-agent with hepatic coma |
| B16.2 | ICD10CM | Acute hepatitis B without delta-agent with hepatic coma |
| B17.11 | ICD10CM | Acute hepatitis C with hepatic coma |
| B19.0 | ICD10CM | Unspecified viral hepatitis with hepatic coma |
| B19.11 | ICD10CM | Unspecified viral hepatitis B with hepatic coma |
| B19.21 | ICD10CM | Unspecified viral hepatitis C with hepatic coma |
| D81.810 | ICD10CM | Biotinidase deficiency |
| E71.110 | ICD10CM | Isovaleric acidemia |
| E71.121 | ICD10CM | Propionic acidemia |
| E72.20 | ICD10CM | Disorder of urea cycle metabolism, unspecified |
| E72.21 | ICD10CM | Argininemia |
| E72.22 | ICD10CM | Arginosuccinic aciduria |
| E72.23 | ICD10CM | Citrullinemia |
| E72.29 | ICD10CM | Other disorders of urea cycle metabolism |
| E72.4 | ICD10CM | Disorders of ornithine metabolism |
| K72.91 | ICD10CM | Hepatic failure, unspecified with coma |
| P74.6 | ICD10CM | Transitory hyperammonemia of newborn |
| Isovaleric acidemia | ||
| E71.110 | ICD10CM | Isovaleric acidemia |
| Ornithine carbamoyltransferase deficiency | ||
| E72.4 | ICD10CM | Disorders of ornithine metabolism |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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