Adult Dosing
Urea cycle disorders
- Administer PO divided tid, each rounded up to nearest 0.5 mL
- Max: 17.5 mL/day
Switching from sodium phenylbutyrate to glycerol phenylbutyrate
- Total daily dose = total daily dosage of sodium phenylbutyrate (g) x 0.86
Phenylbutyrate-naive
- Recommended dose range: 4.5-11.2 mL/m2/day (5-12.4 g/m2/day)
- In patients with some residual enzyme activity who are not adequately controlled with dietary restriction, recommended starting dose is 4.5 mL/m2/day
- Determine starting dose by patient’s residual urea synthetic capacity, dietary protein requirements, and diet adherence
Note: Dosage adjustment and monitoring
Adjustment based on plasma ammonia
- Adjust dose to produce fasting plasma ammonia level less than half ULN according to age
Adjustment based on urinary phenylacetylglutamine
- Each gram of U-PAGN excreted over 24 hr covers waste nitrogen generated from 1.4 grams of dietary protein
- If U-PAGN excretion is insufficient to cover daily dietary protein intake and the fasting ammonia is greater than half the ULN, adjusted dosage upward
- The amount of dose adjustment should factor in the amount of dietary protein that has not been covered (not to exceed 17.5 mL/day)
- Also consider concomitant medications (eg, probenecid) that may decrease urinary excretion of PAGN
Adjustment based on plasma phenylacetate (PPA)
- PAA levels may be useful to guide dosing if symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or intercurrent illness
- Ammonia levels must be monitored closely when changing the dose
- If a high PAA to PAGN ratio exists, a further dosage increase may not increase PAGN formation, even if plasma PAA concentrations are increased, due to saturation of the conjugation reaction
- The PAA to PAGN ratio has been observed to be generally < 1 in patients without significant PAA accumulation
Pediatric Dosing
Urea cycle disorders
- Patients > 2 months
- Administer PO divided tid, each rounded up to nearest 0.5 mL
- Max: 17.5 mL/day
Switching from sodium phenylbutyrate to glycerol phenylbutyrate
- Total daily dose = total daily dosage of sodium phenylbutyrate (g) x 0.8
Phenylbutyrate-naive
- Recommended dose range: 4.5-11.2 mL/m2/day (5-12.4 g/m2/day)
- In patients with some residual enzyme activity who are not adequately controlled with dietary restriction, recommended starting dose is 4.5 mL/m2/day
- Determine starting dose by patient’s residual urea synthetic capacity, dietary protein requirements, and diet adherence
Note: Dosage adjustment and monitoring
Adjustment based on plasma ammonia
- Adjust dose to produce fasting plasma ammonia level less than half ULN according to age
Adjustment based on urinary phenylacetylglutamine
- Each gram of U-PAGN excreted over 24 hr covers waste nitrogen generated from 1.4 grams of dietary protein
- If U-PAGN excretion is insufficient to cover daily dietary protein intake and the fasting ammonia is greater than half the ULN, adjusted dosage upward
- The amount of dose adjustment should factor in the amount of dietary protein that has not been covered (not to exceed 17.5 mL/day)
- Also consider concomitant medications (eg, probenecid) that may decrease urinary excretion of PAGN
Adjustment based on plasma phenylacetate (PPA)
- PAA levels may be useful to guide dosing if symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or intercurrent illness
- Ammonia levels must be monitored closely when changing the dose
- If a high PAA to PAGN ratio exists, a further dosage increase may not increase PAGN formation, even if plasma PAA concentrations are increased, due to saturation of the conjugation reaction
- The PAA to PAGN ratio has been observed to be generally < 1 in patients without significant PAA accumulation
Pregnancy Category:C
Breastfeeding: Safety unknown. It is not known whether the drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into consideration the importance of the drug to the health of the mother.
