Sodium phenylacetate and Sodium benzoate

Sodium phenylacetate and Sodium benzoate is an FDA-registered drug product whose active ingredient is SODIUM PHENYLACETATE AND SODIUM BENZOATE. It is labelled by Zydus Pharmaceuticals USA Inc. taken by intravenous and marketed as a human prescription drug product. Identifiers on file: NDC 70710-1926, application ANDA217526, label effective 20231030. It is one of 3 FDA drug label records sharing the active ingredient SODIUM PHENYLACETATE AND SODIUM BENZOATE. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing SODIUM PHENYLACETATE AND SODIUM BENZOATE are most often described in connection with: sodium phenylacetate, benzoate injection, indicated adjunctive, treatment acute, associated encephalopathy, adult patients, deficiencies enzymes, urea cycle. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Sodium Phenylacetate and Sodium Benzoate Injection is a nitrogen binding agent indicated as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in paediatric and adult patients with deficiencies in enzymes of the urea cycle. ( 1 ) 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) ].

2 DOSAGE AND ADMINISTRATION Sodium Phenylacetate and Sodium Benzoate Injection must be diluted with sterile 10% Dextrose Injection (D10W) before administration. Administration must be through a central venous catheter. Administration through a peripheral line may cause burns. ( 2 ) Sodium Phenylacetate and Sodium Benzoate Injection is administered intravenously as a loading dose infusion administered over 90 to 120 minutes, followed by an equivalent maintenance dose infusion administered over 24 hours. ( 2 ) See Full Prescribing Information for complete dosing recommendations. 2.1 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: Dosage and Administration Abbreviations: CPS - carbamyl phosphate synthetase; OTC - ornithine transcarbamylase; ASS - argininosuccinate synthetase; ASL - argininosuccinate lyase Patient Population Components of Infusion Solution Sodium Phenylacetate and Sodium Benzoate Injection must be diluted with sterile 10% Dextrose Injection at ≥ 25 mL/Kg before administration. Dosage Provided Sodium Phenylacetate and Sodium Benzoate Injection Arginine HCl Injection, 10% Sodium Phenylacetate Sodium Benzoate Arginine HCl CPS and OTC Deficiency Patients 0 to 20 kg: Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 2.5 mL/kg 2 mL/kg 250 mg/kg 250 mg/kg 200 mg/kg ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 2.5 mL/kg 6 mL/kg 250 mg/kg 250 mg/kg 600 mg/kg CPS and OTC Deficiency Patient>20kg: Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 55 mL/m 2 2 mL/kg 5.5g/m 2 5.5 g/m 2 200 mg/kg ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 55 mL/m 2 6 mL/kg 5.5 g/m 2 5.5 g/m 2 600 mg/kg 2.2 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 (8–10 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 (5.1) ]. 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.

4 CONTRAINDICATIONS None ( 4 ) None.

6 ADVERSE REACTIONS 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 compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data were obtained from 316 patients who received Sodium Phenylacetate and Sodium Benzoate Injection as emergency (rescue) or prospective treatment for hyperammonemia as part of an uncontrolled, open-label study. The study population included patients between the ages of 0 to 53 years with a mean (SD) of 6.2 (8.54) years; 51% were male and 49% were female who had the following diagnoses: OTC (46%), ASS (22%), CPS (12%), ASL (2%), ARG (<1%), THN (<1%), and other (18%). Adverse reactions were reported with similar frequency in patients with OTC, ASS, CPS, and diagnoses categorized as "other." Nervous system disorders were more frequent in patients with OTC and CPS, compared with patients with ASS and patients with "other" diagnoses. Convulsions and mental impairment were reported in patients with OTC and CPS. These observations are consistent with literature reports that patients with enzyme deficiencies occurring earlier in the urea cycle (i.e., OTC and CPS) tend to be more severely affected. Adverse reactions profiles differed by age group. Patients ≤30 days of age had more blood and lymphatic system disorders and vascular disorders (specifically hypotension), while patients > 30 days of age had more gastrointestinal disorders (specifically nausea, vomiting and diarrhea). Less common adverse reactions (<3% of patients) that are characterized as severe are listed below by body system. BLOOD AND LYMPHATIC SYSTEM DISORDERS: coagulopathy, pancytopenia, thrombocytopenia. CARDIAC DISORDERS: atrial rupture, bradycardia, cardiac or cardiopulmonary arrest/failure, cardiogenic shock, cardiomyopathy, pericardial effusion. EYE DISORDERS: blindness. GASTROINTESTINAL DISORDERS: abdominal distension, gastrointestinal hemorrhage. GENERAL DISORDERS AND ADMINISTRATION-SITE CONDITIONS: asthenia, brain death, chest pain, multiorgan failure, edema. HEPATOBILIARY DISORDERS: cholestasis, hepatic artery stenosis, hepatic failure/hepatotoxicity, jaundice. INFECTIONS AND INFESTATIONS: sepsis/septic shock. INJURY, POISONING AND PROCEDURAL COMPLICATIONS: brain herniation, subdural hematoma, overdose. INVESTIGATIONS: blood carbon dioxide changes, blood glucose changes, blood pH increased, cardiac output decreased, pCO 2 changes, respiratory rate increased. METABOLISM AND NUTRITION DISORDERS: alkalosis, dehydration, fluid overload/retention, hypoglycemia, hyperkalemia, hypernatremia, alkalosis, tetany. NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED: hemangioma acquired. NERVOUS SYSTEM DISORDERS: areflexia, ataxia, brain infarction, brain hemorrhage, cerebral atrophy, clonus, depressed level of consciousness, encephalopathy, nerve paralysis, intracranial pressure increased, subdural hematoma, tremor. PSYCHIATRIC DISORDERS: acute psychosis, aggression, confusional state, hallucinations. RENAL AND URINARY DISORDERS: anuria, renal failure, urinary retention. RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: acute respiratory distress syndrome, dyspnea, hypercapnia, hyperventilation, Kussmaul respiration, pneumonia aspiration, pneumothorax, pulmonary hemorrhage, pulmonary edema, respiratory acidosis or alkalosis, respiratory arrest/failure. SKIN AND SUBCUTANEOUS TISSUE DISORDERS: alopecia, blister, pruritus generalized, rash, urticarial. VASCULAR DISORDERS: flushing, hemorrhage, hypertension, phlebothrombosis/thrombosis. Table 2 : Adverse Reactions Occurring in ≥3% of Patients Treated with Sodium Phenylacetate and Sodium Benzoate Injection Patients N=316 Number of patients with any adverse event 163 (52%) Blood and lymphatic system disorders 35 (11%) Anemia 12 (4%) Disseminated intravascular coagulation 11 (3%) Cardiac disorders 28 (9%) Gastrointestinal disorders 42 (13%) Diarrhea 10 (3%) Nausea 9 (3%) Vomiting 29 (9%) General disorders and administration-site conditions 45 (14%) Injection-site reaction 11 (3%) Pyrexia 17 (5%) Infections 39 (12%) Urinary tract infection 9 (3%) Injury, poisoning and procedural complications 12 (4%) Investigations 32 (10%) Metabolism and nutrition disorders 67 (21%) Acidosis 8 (3%) Hyperammonemia 17 (5%) Hyperglycemia 22 (7%) Hypocalcemia 8 (3%) Hypokalemia 23 (7%) Metabolic acidosis 13 (4%) Nervous system disorders 71 (22%) Brain edema 17 (5%) Coma 10 (3%) Convulsions 19 (6%) Mental impairment 18 (6%) Psychiatric disorders 16 (5%) Agitation 8 (3%) Renal and urinary disorders 14 (4%) Respiratory, thoracic and mediastinal disorders 47 (15%) Respiratory distress 9 (3%) Skin and subcutaneous tissue disorders 19 (6%) Vascular disorders 19 (6%) Hypotension 14 (4%)

FDA lists 3 drug label records with SODIUM PHENYLACETATE AND SODIUM BENZOATE as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is Sodium phenylacetate and Sodium benzoate used for?
1 INDICATIONS AND USAGE Sodium Phenylacetate and Sodium Benzoate Injection is a nitrogen binding agent indicated as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in paediatric and adult patients with deficiencies in enzymes of the urea cycle. ( 1 ) Sodium Phenylacetate and Sodium Benzoate Injection is indicated as adjunctive therapy in pediatric and …

Who makes Sodium phenylacetate and Sodium benzoate?
Zydus Pharmaceuticals USA Inc. is the labeler of record for Sodium phenylacetate and Sodium benzoate. 3 FDA label records share the active ingredient SODIUM PHENYLACETATE AND SODIUM BENZOATE, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does Sodium phenylacetate and Sodium benzoate come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Sodium phenylacetate and Sodium benzoate prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing SODIUM PHENYLACETATE AND SODIUM BENZOATE?
Yes. 3 FDA drug label records list SODIUM PHENYLACETATE AND SODIUM BENZOATE as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has Sodium phenylacetate and Sodium benzoate been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.