1 INDICATIONS AND USAGE PHEBURANE is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS).

Limitations of Use Episodes of acute hyperammonemia may occur in patients while on PHEBURANE.

PHEBURANE is not indicated for the treatment of acute hyperammonemia, which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

PHEBURANE is a nitrogen-binding agent indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS).

( 1 ) Limitations of Use PHEBURANE is not indicated for the treatment of acute hyperammonemia.

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6 ADVERSE REACTIONS The following adverse reactions associated with the use of sodium phenylbutyrate were identified in clinical studies or postmarketing reports.

Because some of these reactions were reported voluntarily and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Most common adverse reactions (incidence ≥ 3%) are amenorrhea or menstrual dysfunction (irregular menstrual cycles), decreased appetite, body odor and bad taste or taste aversion.

Less Common Clinical Adverse Reactions Blood and lymphatic system disorders: aplastic anemia, ecchymoses Cardiac disorders : arrhythmia Gastrointestinal disorders : abdominal pain, decreased appetite, gastritis, nausea and vomiting, constipation, rectal bleeding, peptic ulcer disease, pancreatitis Metabolism and nutrition disorders: increased weight, edema Nervous system disorders : syncope, headache Psychiatric disorders : depression Renal and urinary disorders : renal tubular acidosis Skin and subcutaneous tissue disorders : rash Laboratory Adverse Reactions Blood and lymphatic system disorders : anemia, leukopenia and leukocytosis, thrombocytopenia, thrombocytosis Hepatobiliary disorders: hyperbilirubinemia, increased blood alkaline phosphatase, increased transaminases Metabolism and nutrition disorders: acidosis, alkalosis, hyperchloraemia, hypophosphataemia, hyperuricemia, hyperphosphatemia, hypernatremia, hypokalemia, hypoalbuminemia, decreased total protein Clinical Adverse Reactions with Use of Phenylacetate Nervous system disorders: Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate, the major metabolite of PHEBURANE (PHEBURANE is not approved for intravenous use or for treatment of patients with cancer).

Signs and symptoms were predominately somnolence, fatigue, and dizziness (lightheadedness); less frequently reported were headache, dysgeusia, hypoacusis, disorientation, memory impairment, and exacerbation of a pre-existing neuropathy.

Most common adverse reactions (incidence ≥ 3%) are menstrual dysfunction, decreased appetite, body odor and bad taste or taste aversion.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Medunik USA, Inc.

at 1-844-884-5520 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .