Acute Hyperammonemia due to NAGS Deficiency
- PO (Adults and Children ): 100–250 mg/kg/day initially, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 100 mg. Should be used with other ammonia lowering treatments including alternate pathway medications, hemodialysis, and protein restriction.
Renal Impairment
- PO (Adults and Children ): eGFR 30–59 mL/min/m2: 50–125 mg/kg/day initially, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 50 mg. Should be used with other ammonia lowering treatments including alternate pathway medications, hemodialysis, and protein restriction. eGFR ≤29 mL/min/m2: 15–60 mg/kg/day initially, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 50 mg. Should be used with other ammonia lowering treatments including alternate pathway medications, hemodialysis, and protein restriction.
Chronic Hyperammonemia due to NAGS Deficiency
- PO (Adults and Children ): 10–100 mg/kg/day, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 100 mg. May be used with other ammonia lowering treatments and protein restriction, based on plasma ammonia levels.
Renal Impairment
- PO (Adults and Children ): eGFR 30–59 mL/min/m2: 5–50 mg/kg/day, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 50 mg. May be used with other ammonia lowering treatments and protein restriction, based on plasma ammonia levels. eGFR ≤29 mL/min/m2: 2–25 mg/kg/day, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 50 mg. May be used with other ammonia lowering treatments and protein restriction, based on plasma ammonia levels.
Acute Hyperammonemia due to PA or MMA
- PO (Adults and Children >15 kg): 3.3 g/m2/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis.
- PO (Adults and Children ≤15 kg): 150 mg/kg/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis.
Renal Impairment
- PO (Adults and Children >15 kg): eGFR 30–59 mL/min/m2: 1.7 g/m2/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis. eGFR ≤29 mL/min/m2: 75 mg/kg/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis.
Renal Impairment
- PO (Adults and Children ≤15 kg): eGFR 30–59 mL/min/m2: 0.55 g/m2/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis. eGFR ≤29 mL/min/m2: 25 mg/kg/day given in 2 divided doses (12 hr apart) immediately before meals/feedings (dose should be rounded to the nearest 50 mg). Continue therapy until ammonia level <50 micromol/L and for a maximum duration of 7 days. Should be used with other ammonia lowering treatments, including IV glucose, insulin, L-carnitine, protein restriction, and dialysis.
Therapeutic Classification: hyperammonemia treatments (due to an enzyme deficiency)
Pharmacologic Classification: enzyme activators
Absorption: 10% absorbed following oral administration.
Distribution: Extensively distributed into extravascular space.
Metabolism/Excretion: Some metabolism by intestinal bacteria; 9% excreted unchanged in urine, 60% excreted unchanged in feces. Metabolic end product (CO2) eliminated via lungs.
Half-Life: 5.6 hr.