FDA label 299188a2-89ec-6aff-e063-6394a90a3cf2

5 WARNINGS AND PRECAUTIONS Neurotoxicity of Phenylacetate : Increased exposure to phenylacetate, the major metabolite of OLPRUVA, may be associated with neurotoxicity in patients with UCDs. Consider reducing the dose if neurotoxicity symptoms are present. ( 5.1 ) Hypokalemia : Renal excretion of phenylacetylglutamine may induce urinary loss of potassium. Monitor serum potassium during therapy and initiate appropriate treatment when necessary. ( 5.2 ) Conditions Associated with Edema : Calculate the total amount of sodium patients will be exposed to based on their body surface area. If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of OLPRUVA and initiate appropriate therapy. ( 5.3 ) 5.1 Neurotoxicity of Phenylacetate Increased exposure to phenylacetate, the major metabolite of OLPRUVA, may be associated with neurotoxicity in patients with UCDs. In a study of adult cancer patients receiving intravenous phenylacetate, 250-300 mg/kg/day for 14 days, repeated at 4-week intervals, signs and symptoms of neurotoxicity, which were reversible upon discontinuation, were seen at plasma concentrations ≥ 3.5 mmol/L, and included somnolence, fatigue, and light headedness [ see Adverse Reactions ( 6 ) ]. OLPRUVA is not approved for intravenous use or for treatment of patients with cancer. If symptoms of vomiting, nausea, headache, somnolence, or confusion are present in the absence of high ammonia levels or other intercurrent illnesses, consider reducing the dose of OLPRUVA [ see Dosage and Administration ( 2.2 ) ]. Phenylacetate caused neurotoxicity when given subcutaneously in rat pups [ see Use in Specific Populations ( 8.4 ) ]. 5.2 Hypokalemia Renal excretion of phenylacetylglutamine may induce urinary loss of potassium. Monitor serum potassium during therapy and initiate appropriate treatment when necessary. 5.3 Conditions Associated with Edema OLPRUVA contains 124 mg (5.4 mmol) of sodium per gram of sodium phenylbutyrate (12.4% w/w) and the Mix-Aid contains 5 mg of sodium per packet, corresponding to 2.5 g (108 mmol) of sodium in the maximum daily dose of 20 g of OLPRUVA. In order to decide if administration of OLPRUVA is appropriate in patients with diseases that involve edema, such as heart failure, cirrhosis, or nephrosis, calculate the total amount of sodium patients will be exposed to based on their BSAs [ see Dosage and Administration ( 2.1 ) ]. If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of OLPRUVA and initiate appropriate therapy.

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 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, 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, hyperchloremia, hypophosphatemia, 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 OLPRUVA (OLPRUVA 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 Acer Therapeutics Inc. at 1-844-600-2237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.