sodium phenylacetate

sodium phenylacetate/sodium benzoate

(soe-dee-um fen-il-as-e-tate/soe-dee-um ben-zo-ate) sodiumphenylacetatesodiumbenzoate,

Ammonul

(trade name)

Classification

Therapeutic: antidotes
Pharmacologic: none assigned

Indications

Adjunctive therapy of acute hyperammonemia associated with urea cycle disorders; when lack of specific enzymes results in an inability to breakdown and eliminate waste nitrogens.

Action

Provides an alternative pathway for nitrogen elimination in patients without a fully functioning urea cycle.

Therapeutic effects

Decreased sequelae of hyperammonemia including encephalopathy and death.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Unknown.Metabolism and Excretion: Metabolized in the liver as part of the alternative pathway in the urea cycle; also metabolized in the kidney.Half-life: Unknown.

Time/action profile (blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	1–3 hr	14–26 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity.Use Cautiously in: Hepatic/renal impairment; Obstetric: Use only if clearly needed; Lactation: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

seizures (life-threatening)
mental impairment

Gastrointestinal

vomiting

Endocrinologic

hyperglycemia

Fluid and Electrolyte

hypokalemia

Interactions

Drug-Drug interaction

Penicillin and probenecid may compete for renal secretion.Valproic acid may contribute to hyperammonemia and negate beneficial effects.

Route/Dosage

Concurrent IV arginine is required.Intravenous (Children 0–20 kg) Loading dose over 90–120 min—2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg sodium benzoate) followed by maintenance infusion—2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg sodium benzoate) over 24 hr, continued until oral therapy is initiated.Intravenous (Children >20 kg) Loading dose over 90–120 min—2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg sodium benzoate) followed by maintenance infusion—55 mL/m²(provides 5.5 g/m² of sodium phenylacetate and 5.5 g/m² sodium benzoate) over 24 hr, continued until oral therapy is initiated.

Availability

Solution for injection (requires dilution): sodium phenylacetate 10% and sodium benzoate injection 10% in 50–mL vials

Nursing implications

Nursing assessment

Assess neurologic status frequently during therapy.
Assess infusion site frequently during therapy. Extravasation into peripheral tissues may lead to skin necrosis. If extravasation is suspected, discontinue infusion and resume at a different site. Treatment of extravasation may include aspiration of residual drug from catheter, limb elevation, and intermittent cooling using cold packs.
Lab Test Considerations: Monitor plasma ammonia levels frequently during therapy.
- Monitor CBC and serum electrolytes frequently during therapy; maintain normal levels. May cause hyperglycemia, hypocalcemia, hypokalemia, and anemia.
- Monitor blood chemistry, pH, and pCO₂ frequently during therapy. May cause metabolic acidosis and hyperammonemia.

Potential Nursing Diagnoses

Risk for injury (Indications)

Implementation

Must be diluted and administered through a central line; administration through peripheral lines may cause burns.
- May cause nausea and vomiting; administer an antiemetic prior to infusion.
- Do not repeat loading dose; phenylacetate plasma levels are prolonged.
- Begin infusion as soon as the diagnosis of hyperammonemia is made.
- Caloric supplementation and restriction of dietary protein are required during therapy. Caloric intake of >80 cal/kg/day should be attempted. Non-protein calories should be supplied as glucose (8–10 mg/kg/min) with Intralipid added.
- Once elevated ammonia levels have been reduced to normal range, oral therapy, such as sodium phenylbutyrate, dietary management and protein restrictions should be started or reinitiated.
Intravenous Administration
Intermittent Infusion: Diluent: Dilute with D10W at ≥25 mL/kg before administration. Use a Millex Durapore GV 33 mm Sterile Syringe Filter (0.22 µm ) during the admixture process when injecting Ammonul into the 10% Dextrose IV bag, regardless of whether particulate matter is seen in the vial; particulate matter may not be seen on visual inspection. Solution is stable for 24 hr at room temperature. Do not administer solutions that are discolored or contain particulate matter.
Rate: Administer loading dose over 90–120 min.
Continuous Infusion: Diluent: Maintenance infusions use same dilution as loading dose and may be continued until elevated plasma ammonia levels have been normalized or patient can tolerate oral nutrition and medications.
Rate: Administer maintenance infusion over 24 hr.
Additive Compatibility: arginine 10%.
Additive Incompatibility: Do not mix or infusion other solutions or medications with sodium phenylacetate and sodium benzoate.

Patient/Family Teaching

Explain purpose of medication to parents/caregivers.

Evaluation/Desired Outcomes

Decreased sequelae of hyperammonemia including encephalopathy and death.

sodium phenylacetate