Sodium phenylacetate and Sodium benzoate
Generic: SODIUM PHENYLACETATE AND SODIUM BENZOATE
Basic Information
Manufacturer
Navinta LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
d20768fe-4516-483a-a082-ff1df9ad1d99
Indications & Usage
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 pediatric 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) ].
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) ].
Adverse Reactions
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 Navinta LLC at 1-609-883-1135 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%)
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Navinta LLC at 1-609-883-1135 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%)