SODIUM PHENYLACETATE AND SODIUM BENZOATE

The pharmacokinetics of intravenously administered Sodium Phenylacetate and Sodium Benzoate Injection was characterized in healthy adult volunteers. Both benzoate and phenylacetate exhibited nonlinear kinetics. Following 90 minute intravenous infusion mean AUC last for benzoate was 20.3, 114.9, 564.6, 562.8, and 1599.1 mcg/mL following doses of 1, 2, 3.75, 4, and 5.5 g/m 2 , respectively. The total clearance decreased from 5.19 to 3.62 L/h/m 2 at the 3.75 and 5.5 g/m 2 doses, respectively. Simil...

The efficacy of Sodium Phenylacetate and Sodium Benzoate Injection in improving patient survival of acute hyperammonemic episodes was demonstrated in an analysis of 316 patients (1045 episodes of hospitalization) treated between 1981 and 2003. The demographic characteristics and diagnoses of the patient population are shown in Table 3.

Table 3Baseline Characteristics and Diagnoses of Study Population OTC = ornithine transcarbamylase deficiency ASS = argininosuccinate synthetase deficiency CPS = carbamyl phosphate synthetase deficiency ASL = argininosuccinate lyase deficiency ARG = arginase d...

The most frequently reported adverse reactions (incidence ≥ 6%) are vomiting, hyperglycemia, hypokalemia, convulsions, and mental impairment. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals USA Inc. Pennington, NJ 08534 at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly...

None ( 4 ) None.

Decreased Potassium Levels: Plasma potassium levels should be carefully monitored and appropriate treatment given when necessary. ( 5.1 ) Conditions Associated with Fluid Overload: Sodium Phenylacetate and Sodium Benzoate Injection contains 30.5 mg of sodium per mL of undiluted product. Caution should be used if Sodium Phenylacetate and Sodium Benzoate Injection is administered to patients with congestive heart failure, severe renal insufficiency, or with conditions in which there is sodium rete...

7 DRUG INTERACTIONS Some antibiotics such as penicillin may affect the overall disposition of the infused drug. ( 7 ) Probenecid may affect renal excretion of phenylacetylglutamine and hippurate. ( 7 ) Valproic acid given to patients with urea cycle disorders may exacerbate their condition and antagonize the efficacy of Sodium Phenylacetate and Sodium Benzoate Injection through inhibition of the s...