FDA

Sodium Phenylacetate and Sodium Benzoate

Approved 10 Jun 2021IntravenousSolution

The FDA lists this product in 5 strengths and forms.

Indications

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) ].

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 pediatric and adult patients with deficiencies in enzymes of the urea cycle.

Contraindications

None None.

Warnings and precautions

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 retention with edema.

(5.2) Extravasation : Extravasation of Sodium Phenylacetate and Sodium Benzoate Injection into the perivenous tissues during high flow bolus infusion may lead to skin necrosis, especially in infants. The infusion site must be monitored closely for possible tissue infiltration during drug administration. (5.3) Neurotoxicity of Phenylacetate: Because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies, repeat loading doses should not be administered.

Additionally, neurotoxicity related to phenylacetate has been reported in cancer patients. Monitor patients for symptoms of acute neurotoxicity. (5.4) Hyperventilation and Metabolic Acidosis: Sodium Phenylacetate and Sodium Benzoate Injection may cause side effects typically associated with salicylate overdose, such as hyperventilation and metabolic acidosis. Monitor patient blood chemistry profiles and perform frequent blood pH and pCO2 measurements.

Indications

Warnings and precautions

Adverse reactions

The most frequently reported adverse reactions (incidence ≥6%) are vomiting, hyperglycemia, hypokalemia, convulsions, and mental impairment To report SUSPECTED ADVERSE REACTIONS, contact MAIA Pharmaceuticals, Inc. at 1-888-877-9064 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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, pCO2 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, urticaria VASCULAR DISORDERS: flushing, hemorrhage, hypertension, phlebothrombosis/thrombosis Table 2

Sodium Phenylacetate and Sodium Benzoate

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Sodium Phenylacetate and Sodium Benzoate

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Decreased Potassium Levels

5.2Conditions Associated with Fluid Overload Sodium Phenylacetate and Sodium Benzoate

5.3Extravasation

5.4Neurotoxicity of Phenylacetate Because

5.5Hyperventilation and Metabolic Acidosis Due

Interactions

Pregnancy and breastfeeding

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information

At a glance