Sodium benzoate and sodium phenylacetate

Renal Impairment The drug metabolites of Sodium Phenylacetate and Sodium Benzoate Injection (phenylacetylglutamine and hippurate) and subsequently ammonia are primarily excreted by the kidney. Therefore, use caution and closely monitor patients with impaired renal function who receive Sodium Phenylacetate and Sodium Benzoate Injection.

Recommended Dosage Sodium Phenylacetate and Sodium Benzoate Injection must be diluted with sterile 10% Dextrose Injection (D10W) before administration. The dilution and dosage of Sodium Phenylacetate and Sodium Benzoate Injection are determined by weight for neonates, infants and young children, and by body surface area for larger patients, including older children, adolescents, and adults (Table 1).

Table 1

Administration Sodium Phenylacetate and Sodium Benzoate Injection is a concentrated solution and must be diluted before intravenous administration via a central venous catheter. Administration through a peripheral intravenous catheter may cause burns. Sodium Phenylacetate and Sodium Benzoate Injection may not be administered by any other route.

Sodium Phenylacetate and Sodium Benzoate Injection should be administered as a loading dose infusion over 90 to 120 minutes, followed by the same dose repeated as a maintenance infusion administered over 24 hours. Because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies, repeat loading doses of Sodium Phenylacetate and Sodium Benzoate Injection should not be administered.

Maintenance infusions may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications. An antiemetic may be administered during Sodium Phenylacetate and Sodium Benzoate Injection infusion to aid control of infusion-associated nausea and vomiting. Administration of analogous oral drugs, such as sodium phenylbutyrate, should be terminated prior to Sodium Phenylacetate and Sodium Benzoate Injection infusion.

Sodium Phenylacetate and Sodium Benzoate Injection infusion should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. Non-protein calories should be supplied principally as glucose (8 to 10 mg/kg/min) with an intravenous fat emulsion added.

Attempts should be made to maintain a caloric intake of greater than 80 kcal/kg/day. During and after infusion of Sodium Phenylacetate and Sodium Benzoate Injection, ongoing monitoring of the following clinical laboratory values is crucial: plasma ammonia, glutamine, quantitative plasma amino acids, blood glucose, electrolytes, venous or arterial blood gases, AST and ALT.

On-going monitoring of the following clinical responses is also crucial to assess patient response to treatment: neurological status, Glasgow Coma Scale, tachypnea, CT or MRI scan or fundoscopic evidence of cerebral edema, and/or of gray matter and white matter damage. Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration [ see Warnings and Precautions ].

In the non-neonatal study patient population treated with Sodium Phenylacetate and Sodium Benzoate Injection, dialysis was required in 13% of hyperammonemic episodes. Standard hemodialysis was the most frequently used dialysis method. High levels of ammonia can be reduced quickly when Sodium Phenylacetate and Sodium Benzoate Injection is used with hemodialysis, as the ammonia-scavenging of Sodium Phenylacetate and Sodium Benzoate Injection suppresses the production of ammonia from catabolism of endogenous protein and hemodialysis eliminates the ammonia and ammonia conjugates.

Sodium Phenylacetate and Sodium Benzoate Injection solutions are physically and chemically stable for up to 24 hours at room temperature and room lighting conditions. No compatibility information is presently available for Sodium Phenylacetate and Sodium Benzoate Injection infusion solutions except for Arginine HCl Injection, 10%, which may be mixed in the same container as Sodium Phenylacetate and Sodium Benzoate Injection.

Other infusion solutions and drug products should not be administered together with Sodium Phenylacetate and Sodium Benzoate Injection infusion solution. Sodium Phenylacetate and Sodium Benzoate Injection solutions may be prepared in glass and PVC containers. Arginine Administration Intravenous arginine is an essential component of therapy for patients with carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or argininosuccinate lyase (ASL) deficiency.

Because hyperchloremic acidosis may develop after high- dose arginine hydrochloride administration, chloride and bicarbonate levels should be monitored and appropriate amounts of bicarbonate administered. In hyperammonemic infants with suspected, but unconfirmed urea cycle disorders, intravenous arginine should be given (6 mL/kg of Arginine HCl Injection 10%, over 90 minutes followed by the same dose given as a maintenance infusion over 24 hours).

If deficiencies of ASS or ASL are excluded as diagnostic possibilities, the intravenous dose of Arginine HCl should be reduced to 2 mL/kg/day Arginine HCl Injection 10%. Converting to Oral Treatment Once elevated ammonia levels have been reduced to the normal range, oral therapy, such as sodium phenylbutyrate, dietary management and maintenance protein restrictions should be started or reinitiated.