Usual Adult Dose for Hyperammonemia

For the Treatment of Acute or Chronic Hyperammonemia due to NAGS (N-acetylglutamate synthase) Deficiency:

• Acute Hyperammonemia: 100 to 250 mg/kg/day orally
• Chronic Hyperammonemia: 10 to 100 mg/kg/day orally

• Daily doses should be divided and administered 2 to 4 times a day; doses should be rounded to the nearest 100 mg.
• During acute hyperammonemic episodes, this drug should be administered with other ammonia lowering therapies, such as alternate pathway medications, hemodialysis, and protein restriction.
• For administration during chronic therapy, concomitant use of other ammonia lowering therapies and protein restriction may be needed based on plasma ammonia levels.
• Plasma ammonia levels should be closely monitored and doses titrated to maintain plasma ammonia levels within the normal range

• Weight greater than 15 kg: 3.3 g/m2/day
• Weight 15 kg or less: 150 mg/kg/day

• Daily doses should be given in 2 equally divided doses 12 hours apart; doses should be rounded up to the nearest 50 mg.
• Treatment should continue until the ammonia level is less than 50 micromol/L and for a maximum duration of 7 days.
• During acute hyperammonemic episodes, administer with other ammonia lowering therapies, such as intravenous glucose, insulin, L-carnitine, protein restriction, and dialysis.

• For NAGS deficiency, treatment should be initiated as soon as the diagnosis of NAGS deficiency is suspected, which may be as soon as at birth, and managed by a physician and medical team experienced in metabolic disorders.
• For acute hyperammonemia due to PA or MMA, initiate treatment with a suspected or confirmed diagnosis of PA or MMA.

• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to NAGS deficiency.
• Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.
• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to PA or MMA.

Usual Pediatric Dose for Hyperammonemia

For the Treatment of Acute or Chronic Hyperammonemia due to NAGS (N-acetylglutamate synthase) Deficiency:

• Acute Hyperammonemia: 100 to 250 mg/kg/day orally
• Chronic Hyperammonemia: 10 to 100 mg/kg/day orally

• Daily doses should be divided and administered 2 to 4 times a day; doses should be rounded to the nearest 100 mg.
• During acute hyperammonemic episodes, this drug should be administered with other ammonia lowering therapies, such as alternate pathway medications, hemodialysis, and protein restriction.
• For administration during chronic therapy, concomitant use of other ammonia lowering therapies and protein restriction may be needed based on plasma ammonia levels.
• Plasma ammonia levels should be closely monitored and doses titrated to maintain plasma ammonia levels within the normal range

• Weight greater than 15 kg: 3.3 g/m2/day
• Weight 15 kg or less: 150 mg/kg/day

• Daily doses should be given in 2 equally divided doses 12 hours apart; doses should be rounded up to the nearest 50 mg.
• Treatment should continue until the ammonia level is less than 50 micromol/L and for a maximum duration of 7 days.
• During acute hyperammonemic episodes, administer with other ammonia lowering therapies, such as intravenous glucose, insulin, L-carnitine, protein restriction, and dialysis.

• For NAGS deficiency, treatment should be initiated as soon as the diagnosis of NAGS deficiency is suspected, which may be as soon as at birth, and managed by a physician and medical team experienced in metabolic disorders.
• For acute hyperammonemia due to PA or MMA, initiate treatment with a suspected or confirmed diagnosis of PA or MMA.

• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to NAGS deficiency.
• Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.
• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to PA or MMA.

Renal Dose Adjustments

Mild renal impairment (eGFR 60 mL/min/1.73 m2 or greater): No adjustment recommended
Moderate renal impairment (eGFR 30 to 59 mL/min/1.73 m2):

• Acute hyperammonemia due to NAGS deficiency: 50 to 125 mg/kg/day orally divided into 2 to 4 doses and rounded to the nearest 50 mg
• Chronic hyperammonemia due to NAGS deficiency: 5 to 50 mg/kg/day orally divided into 2 to 4 doses and rounded to the nearest 50 mg
• Acute hyperammonemia due to PA or MMA: 1.7 g/m2/day (for patients weight greater than 15 kg) or 75 mg/kg/day (for patients weighing 15 kg or less) orally in 2 equally divided doses every 12 hours; doses should be rounded up to nearest 50 mg

• Acute hyperammonemia due to NAGS deficiency: 15 to 60 mg/kg/day orally divided into 2 to 4 doses and rounded to the nearest 50 mg
• Chronic hyperammonemia due to NAGS deficiency: 2 to 25 mg/kg/day orally divided into 2 to 4 doses and rounded to the nearest 50 mg
• Acute hyperammonemia due to PA or MMA: 0.55 g/m2/day (for patients weighing greater than 15 kg) or 25 mg/kg/day (for patients weighing 15 kg or less) orally in 2 equally divided doses every 12 hours; doses should be rounded up to nearest 50 mg

Liver Dose Adjustments

Data not available

Dose Adjustments

Therapeutic Monitoring For NAGS Deficiency:

• Closely monitor plasma ammonia levels, doses should be titrated to maintain ammonia level within normal range for patient's age and clinical condition

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in geriatric population.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Tablets must be dispersed in water; do not swallow whole or crushed
• Take orally prior to meals or feedings
• Follow preparation instructions below; use in foods or liquids other than water has not been studied and is not recommended

• Add a minimum of 2.5 mL of water in cup for each 200-mg tablet, each half (100-mg) tablet, or each quarter (50 mg) tablet needed for the prescribed dose
• Add tablet(s) to the water and carefully stir tablet and water mixture
• Swallow mixture immediately; rinse cup with additional water and swallow immediately; repeat as needed until no pieces of tablet are left in cup
• The mixture has a slightly acid taste (slightly sour)

• Add a minimum of 2.5 mL of water in cup for each 200-mg tablet, each half (100-mg) tablet, or each quarter (50 mg) tablet needed for the prescribed dose
• Add tablet(s) to the water and carefully stir tablet and water mixture
• Draw mixture into a catheter-tip syringe
• Administer mixture immediately through the NG or G-tube; flush immediately with 1 or 2 mL of additional water to clear tube; flush tube as needed until no pieces of tablet are left in syringe or feeding tube

• Add a minimum of 2.5 mL of water in cup for each 200-mg tablet, each half (100-mg) tablet, or each quarter (50 mg) tablet needed for the prescribed dose
• Add tablet(s) to the water and carefully stir tablet and water mixture
• Draw mixture into oral syringe
• Administer mixture immediately; refill oral syringe with a minimum of 1 to 2 mL of additional water and administer immediately; flush oral syringe until no pieces of tablet are left in syringe

• Date container with date of opening; discard 1 month after opening
• Keep container tightly closed between openings to protect from moisture

• This drug should be managed by a physician and medical team experienced in metabolic disorders.

• Monitor plasma ammonia levels

• Advise patient/caregivers to read the US FDA-approved patient labeling (Instructions for Use).
• Ensure patient/caregivers are aware of administration and storage requirements.