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/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⬆⬇
(plasma concentrations)
ROUTE
ONSET
PEAK
DURATION
IV
rapid
1–3 hr
14–26 hr
Contraind./Precautions⬆⬇
Contraindicated in:
Hypersensitivity.
Use Cautiously in:
Hepatic impairment;
Renal impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.
Valproic acid may contribute to hyperammonemia and negate beneficial effects.
Route/Dosage⬆⬇
Concurrent IV arginine is required.
IV (Children 0–20 kg): Loading dose: 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.
IV (Children >20 kg): Loading dose: 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.
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.
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 kcal/kg/day should be attempted. Nonprotein calories should be supplied as glucose (8–10 mg/kg/min) with Intralipid added.
Once ↑ ammonia levels have been reduced to normal range, oral therapy, such as sodium phenylbutyrate; dietary management; and protein restrictions should be started or reinitiated.
IV 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 m) 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 Incompatibility: Do not administer other drugs through same IV line.
Patient/Family Teaching⬆⬇
Explain purpose and side effects of medication to patient.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient of adverse reactions such as vomiting, hyperglycemia, hypokalemia, convulsions, and mental impairment.
Instruct patient that when plasma ammonia levels normalize, dietary protein intake can be ↑ with the goal of unrestricted protein intake.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Evaluation/Desired Outcomes⬆⬇
Decreased sequelae of hyperammonemia including encephalopathy and death.