- 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
- 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
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
- 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
- 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
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
