Recommended Dosage for Acute or Chronic Hyperammonemia due to NAGS Deficiency

Treatment Initiation
Initiate CARBAGLU treatment 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.

Dosage for Acute Hyperammonemia due to NAGS Deficiency

• The recommended daily dosage of CARBAGLU in pediatric and adult patients for acute hyperammonemia due to NAGS deficiency is 100 mg/kg to 250 mg/kg.
• Divide the daily dosage into 2 to 4 doses and round to the nearest 100 mg (i.e., half of a CARBAGLU tablet).
• During acute hyperammonemic episodes, administer CARBAGLU with other ammonia lowering therapies, such as alternate pathway medications, hemodialysis, and protein restriction.
  

Dosage for Chronic Hyperammonemia due to NAGS Deficiency

• The recommended daily dosage of CARBAGLU in pediatric and adult patients for chronic hyperammonemia due to NAGS deficiency is 10 mg/kg to 100 mg/kg.
• Divide the daily dosage into 2 to 4 doses and round to the nearest 100 mg (i.e., half of a CARBAGLU tablet).
  
• During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be needed based on plasma ammonia levels.
  

Therapeutic Monitoring
Closely monitor plasma ammonia levels. Titrate the CARBAGLU dosage to maintain the plasma ammonia level within the normal range for the patient's age, taking into consideration their clinical condition (e.g., nutritional requirements, protein intake, growth parameters, etc.).

Adjust the recommended dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.3)].

Recommended Dosage for Acute Hyperammonemia due to PA or MMA

​Treatment Initiation
Initiate CARBAGLU for the treatment of acute hyperammonemia in patients with a suspected or confirmed diagnosis of PA or MMA.

​Dosage for Acute Hyperammonemia due to PA or MMA

• ​The recommended daily dosage of CARBAGLU in pediatric and adult patients with acute hyperammonemia due to PA or MMA is:
  • ​150 mg/kg/day for patients less than or equal to 15 kg
  • ​3.3 g/m2/day for patients greater than 15 kg
    
• ​Divide the daily dosage into 2 equal doses and round up to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet). Administer doses 12 hours apart.
• ​Continue CARBAGLU treatment until the patient's ammonia level is less than 50 micromol/L and for a maximum duration of 7 days.
  
• ​During acute hyperammonemic episodes, administer CARBAGLU with other ammonia lowering therapies, such as intravenous glucose, insulin, L-carnitine, protein restriction, and dialysis.

​Adjust the recommended dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.3)].

Dosage Adjustment in Patients with Renal Impairment

​No dosage adjustment is warranted in patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m2). The recommended dosage of CARBAGLU in patients with moderate or severe renal impairment is shown below.

Preparation and Administration

​Overview

• ​Disperse CARBAGLU tablets in water. Do not swallow whole or crushed.
• ​CARBAGLU tablets do not dissolve completely in water, and undissolved particles of the tablet may remain in the mixing container.
• ​Take CARBAGLU immediately before meals or feedings.
  
• ​The CARBAGLU suspension has a slightly acidic taste.
  
• ​For all preparations, use in foods or liquids other than water has not been studied and is not recommended.
  

​Oral Administration
For oral administration, administer CARBAGLU as follows:

• ​Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose.
• ​Add the CARBAGLU tablets to the water in the cup.
• ​Carefully stir the tablet and water mixture.
  
• ​Swallow the mixture immediately. Pieces of the tablet may remain in the cup.
  
• ​Rinse the cup with additional water and swallow the mixture immediately. Repeat as needed until no pieces of the tablet are left in the cup.
  

​Use of an Oral Syringe for Oral Administration
For administration via an oral syringe, administer CARBAGLU as follows:

• ​Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose.
• ​Add the CARBAGLU tablets to the water in the cup.
• ​Carefully stir the tablet and water mixture.
  
• ​Draw up the mixture in an oral syringe and administer immediately. Pieces of the tablet may remain in the oral syringe.
  
• ​Refill the oral syringe with a minimum volume of water (1 mL to 2 mL) and administer immediately.
  
• ​Flush the oral syringe again, as needed, until no pieces of the tablet are left in the syringe.
  

​Use of Nasogastric Tube (NG Tube) or Gastrostomy Tube (G-Tube) for Feeding Tube Administration

​For patients who have a NG tube or G-tube in place, administer CARBAGLU as follows:

• ​Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose.
• ​Add the CARBAGLU tablets to the water in the cup.
• ​Carefully stir the tablet and water mixture.
  
• ​Draw up the mixture into a catheter-tip syringe.
  
• ​Administer the mixture immediately through the NG tube or G-tube. Pieces of the tablet may remain in the catheter-tip syringe or the feeding tube.
  
• ​Flush immediately with 1 to 2 mL of additional water to clear the NG tube or G-tube.
  
• ​Flush the NG tube or G-tube again, as needed, until no pieces of the tablet are left in the syringe or the feeding tube.