Drug Information for AMMONUL (sodium phenylacetate and sodium benzoate) Injection 10% / 10% (Ucyclyd Pharma Inc.): ADVERSE REACTIONS

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  • The safety data were obtained from 316 patients who received AMMONUL® 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%).

    Table 2 Adverse Events Occurring in = 3% of Patients Treated with AMMONUL®
    PatientsN=316
    No. patients with any adverse event163 (52%)
    Blood and lymphatic system disorders35 (11%)
    Anemia NOS12 (4%)
    Disseminated intravascular coagulation11 (3%)
    Cardiac disorders28 (9%)
    Gastrointestinal disorders42 (13%)
    Diarrhea NOS10 (3%)
    Nausea9 (3%)
    Vomiting NOS29 (9%)
    General disorders and administration-site conditions45 (14%)
    Injection-site reaction NOS11 (3%)
    Pyrexia17 (5%)
    Infections39 (12%)
    Urinary tract infection NOS9 (3%)
    Injury, poisoning and procedural complications12 (4%)
    Investigations32 (10%)
    Metabolism and nutrition disorders67 (21%)
    Acidosis NOS8 (3%)
    Hyperammonemia17 (5%)
    Hyperglycemia NOS22 (7%)
    Hypocalcemia8 (3%)
    Hypokalemia23 (7%)
    Metabolic acidosis NOS13 (4%)
    Nervous system disorders71 (22%)
    Brain edema17 (5%)
    Coma10 (3%)
    Convulsions NOS19 (6%)
    Mental impairment NOS18 (6%)
    Psychiatric disorders16 (5%)
    Agitation8 (3%)
    Renal and urinary disorders14 (4%)
    Respiratory, thoracic and mediastinal disorders47 (15%)
    Respiratory distress9 (3%)
    Skin and subcutaneous tissue disorders19 (6%)
    Vascular disorders19 (6%)
    Hypotension NOS14 (4%)
  • Clinically Important Adverse Reactions

  • Adverse events occurred most frequently in the following system organ classes: nervous system disorders (22% of patients), metabolism and nutrition disorders (21% of patients), and respiratory, thoracic and mediastinal disorders (15% of patients). The most frequently reported adverse events were vomiting (9% of patients), hyperglycemia (7% of patients), hypokalemia (7% of patients), convulsions (6% of patients), and mental impairment (6% of patients).

    Adverse events leading to study drug discontinuation occurred in 4% of patients. Metabolic acidosis and injection-site reactions each led to discontinuation in 2 patients (< 1%). Adverse events leading to discontinuation in 1 patient included bradycardia, abdominal distension, injection-site extravasation, injection-site hemorrhage, blister, overdose, subdural hematoma, hyperammonemia, hypoglycemia, clonus, coma, increased intercranial pressure, hypercapnia, Kussmaul respiration, respiratory distress, respiratory failure, pruritis, and maculo-papular rash.

  • Subpopulation and Risk Factor Data

  • Adverse events 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 event profiles did differ 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).

  • Other Less Common Adverse Events Occurring in < 3% of Patients

  • Less common adverse events that could represent drug-induced reactions or are characterized as severe are listed below by body system.

    BLOOD AND LYMPHATIC SYSTEM DISORDERS: coagulopathy, pancytopenia, thrombocytopenia

    CARDIAC DISORDERS: atrial rupture, cardiac or cardiopulmonary arrest/failure, cardiogenic shock, cardiomyopathy, pericardial effusion

    EYE DISORDERS: blindness

    GASTROINTESTINAL DISORDERS: 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

    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, 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, 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, pruritis generalized, rash, urticaria

    VASCULAR DISORDERS: flushing, hemorrhage, hypertension, phlebothrombosis/thrombosis

  • Drug Information Provided by National Library of Medicine (NLM).
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