SODIUM PHENYLBUTYRATE Drug Interactions: What You Need to Know

INTERACTIONS Valproic Acid, Haloperidol, or Corticosteroids : May increase plasma ammonia level; monitor ammonia levels closely. ( 7.1 ) Probenecid : May inhibit renal excretion of metabolites of PHEBURANE including phenylacetate and phenylacetylglutamine; monitor for potential neurotoxicity. ( 7.2 )

7.1 Potential for Other Drugs to Affect Ammonia Corticosteroids Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.

Valproic

Acid and Haloperidol Hyperammonemia may be induced by haloperidol and by valproic acid. Monitor plasma ammonia levels closely when corticosteroids, valproic acid, or haloperidol is used concomitantly with PHEBURANE.

7.2 Potential for Other Drugs to Affect PHEBURANE Probenecid Probenecid may inhibit renal excretion of the metabolites of PHEBURANE including phenylacetate and phenylacetylglutamine. Monitor patients for potential neurotoxicity and measure plasma phenylacetate and phenylacetylglutamine levels when probenecid is used concomitantly with PHEBURANE <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span> .

CONTRAINDICATIONS Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.

AND PRECAUTIONS Neurotoxicity of Phenylacetate : Increased exposure to phenylacetate, the major metabolite of PHEBURANE, 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 weight or body surface area. If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of PHEBURANE and initiate appropriate therapy. ( 5.3 )

Diabetes

Mellitus, Hereditary Fructose Intolerance, Glucose-Galactose Malabsorption or Sucrase-Isomaltase Insufficiency : Avoid use of PHEBURANE in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency. ( 5.4 )

5.1 Neurotoxicity of Phenylacetate Increased exposure to phenylacetate, the major metabolite of PHEBURANE, 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 ) ]</span> . PHEBURANE 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 PHEBURANE <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span> . Phenylacetate caused neurotoxicity when given subcutaneously in rat pups <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.4 )]</span> .

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 PHEBURANE contains 124 mg (5.4 mmol) of sodium per gram of sodium phenylbutyrate, corresponding to 2.5 g (108 mmol) of sodium in the maximum daily dose of 20 g of sodium phenylbutyrate. In order to decide if administration of PHEBURANE 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 weight or body surface area (BSA) <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span> . If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of PHEBURANE and initiate appropriate therapy.

5.4 Diabetes Mellitus, Hereditary Fructose Intolerance, Glucose-Galactose Malabsorption or Sucrase-Isomaltase Insufficiency PHEBURANE contains 768 mg of sucrose per gram of sodium phenylbutyrate, corresponding to 15.4 g of sucrose in the maximum daily dose of 20 g of sodium phenylbutyrate. This should be considered in patients with diabetes mellitus. Avoid use of PHEBURANE in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.