WARNINGS
Each BUPHENYL® Tablet contains 62 mg of sodium (9.2% w/w) (corresponding to 124 mg of sodium per gram of sodium phenylbutyrate [12.4% w/w]) and BUPHENYL Powder contains 11.7 grams of sodium per 100 grams of powder, corresponding to 125 mg of sodium per gram of sodium phenylbutyrate (12.4% w/w). BUPHENYL should be used with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema.
Because BUPHENYL is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted by the kidney, use caution when administering the drug to patients with hepatic or renal insufficiency or inborn errors of beta oxidation. Probenecid is known to inhibit the renal transport of many organic compounds, including hippuric acid, and may affect renal excretion of the conjugated product of BUPHENYL as well as its metabolite.
Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.
PRECAUTIONS
General
BUPHENYL® should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation.
There have been published reports of hyperammonemia being induced by haloperidol and by valproic acid.
Neurotoxicity of phenylacetate in animals
When given subcutaneously to rat pups, 190–474 mg/kg phenylacetate caused decreased proliferation and increased loss of neurons, and it reduced CNS myelin. Cerebral synapse maturation was retarded, and the number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth. Prenatal exposure of rat pups to phenylacetate produced lesions in layer 5 of the cortical pyramidal cells; dendritic spines were longer and thinner than normal and reduced in number.
Information for Patients
The full text of the separate insert of information for patients is reprinted at the end of the labeling.
Laboratory Tests
Plasma levels of ammonia, arginine, branched-chain amino acids, and serum proteins should be maintained within normal limits, and plasma glutamine should be maintained at levels less than 1,000 µmol/L. Serum drug levels of phenylbutyrate and its metabolites, phenylacetate and phenylacetylglutamine, should be monitored periodically.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and fertility studies of sodium phenylbutyrate have not been conducted.
Pregnancy
Pregnancy Category C.
Animal reproduction studies have not been conducted with BUPHENYL®. It is also not known whether BUPHENYL can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
BUPHENYL should be given to a pregnant woman only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BUPHENYL® is administered to a nursing woman.
Pediatric Use
The use of tablets for neonates, infants and children to the weight of 20 kg is not recommended. (See Dosage and Administration.)
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