Sodium Phenylacetate and Sodium Benzoate Injection

AMMONUL (sodium phenylacetate and sodium benzoate) Injection 10% per 10% (a nitrogen binding agent), is a sterile, concentrated, aqueous solution of sodium phenylacetate and sodium benzoate. The pH of the solution is between 6 and 8. Sodium phenylacetate is a crystalline, white to off-white powder with a strong, offensive odor. It is soluble in water. Sodium benzoate is a white and odorless, crystalline powder that is readily soluble in water.

Figure 1

Sodium phenylacetate has a molecular weight of 158.13 and the molecular formula C8H7NaO2. Sodium benzoate has a molecular weight of 144.11 and the molecular formula C7H5NaO2.

Each mL of AMMONUL contains 100 mg of sodium phenylacetate and 100 mg of sodium benzoate, and Water for Injection. Sodium hydroxide and/or hydrochloric acid may have been used for pH adjustment.

AMMONUL injection is a sterile, concentrated solution intended for intravenous administration via a central line only after dilution [see DOSAGE AND ADMINISTRATION].

Dosage Forms And Strengths

AMMONUL (sodium phenylacetate and sodium benzoate) Injection 10% per 10% is a sterile, concentrated, aqueous solution of sodium phenylacetate and sodium benzoate.

Storage And Handling

AMMONUL (sodium phenylacetate and sodium benzoate) Injection 10% per 10% is supplied in a single use glass vial.

NDC 62592-720-50 single use vial containing 50 mL of sodium phenylacetate and sodium benzoate injection 10% per 10%.

Storage

Store at 25°C (77°F), excursions permitted to 15° - 30°C (59°- 86°F).

Manufactured by: Cangene bioPharma, Inc., Baltimore, MD 21230. Manufactured for: Ucyclyd Pharma, Inc., a wholly-owned subsidiary of Medicis Pharmaceutical Corp., 7720 N. Dobson, Road, Scottsdale, AZ 85256. Revised: Aug 2013

Physicians should advise patients and caregivers about the following for safe use of AMMONUL:

• When plasma ammonia levels have normalized, dietary protein intake can usually be increased with the goal of unrestricted protein intake.
• Caution should be exercised when AMMONUL is administered to a nursing woman.
• The most common adverse reactions are vomiting, hyperglycemia, hypokalemia, convulsions, and mental impairment.
• Generally BUPHENYL is stopped during the time AMMONUL is used.

Sodium Phenylacetate and Sodium Benzoate Injection is indicated as adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. During acute hyperammonemic episodes, arginine supplementation, caloric supplementation, dietary protein restriction, hemodialysis, and other ammonia lowering therapies should be considered [see Warnings and Precautions (5)].

Sodium Phenylacetate and Sodium Benzoate Injection 10% per 10% is a sterile, concentrated, aqueous solution of sodium phenylacetate and sodium benzoate.

Formal drug interaction studies have not been performed with Sodium Phenylacetate and Sodium Benzoate Injection.

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 Sodium Phenylacetate and Sodium Benzoate Injection.

Use of corticosteroids may cause a protein catabolic state and, thereby, potentially increase plasma ammonia levels in patients with impaired ability to form urea.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Sodium Phenylacetate and Sodium Benzoate Injection. Studies to evaluate the possible impairment of fertility or mutagenic potential of Sodium Phenylacetate and Sodium Benzoate Injection have not been performed. Results indicate that sodium benzoate is not mutagenic or carcinogenic, and does not impair fertility.

Animal Toxicology and/or Pharmacology

In animal studies, subcutaneous administration to rat pups of 190– 474 mg/kg of phenylacetate caused decreased proliferation and increased loss of neurons, and reduced central nervous system (CNS) myelin. Cerebral synapse maturation was retarded, and the number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth. Pregnant rats were given phenylacetate at 3.5 µmol/g/day subcutaneously from gestation day 7 through normal delivery. Prenatal exposure of rat pups to phenylacetate produced lesions in layer 5 cortical pyramidal cells; dendritic spines were longer and thinner than normal and reduced in number.

Sodium Phenylacetate and Sodium Benzoate Injection 10% per 10% is supplied in a single use glass vial.

NDC 68682-001-50 single use vial containing 50 mL of Sodium Phenylacetate and Sodium Benzoate Injection 10% per 10%.

Storage: Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).