NEODOSE

INDICATIONS

• Treatment of hyperammonemia due to various metabolic disorders: Based upon use in newborns from case reports, carglumic acid, when administered in addition to standard therapy, acutely reduces plasma ammonia levels in patients with branched-chain organic acidemias, such as methylmalonic aciduria (MMA), propionic aciduria (PA), and isovaleric acidemia (IVA) . In these metabolic disorders, synthesis of N-acetylglutamate is inhibited due to the build up of the respective branched-chain organic acid; once standard therapy has corrected the acidemia, hyperammonemia is also resolved. Doses used in these cases ranged from 70 to 200 mg/kg/day, administered as a single dose or over a 48-hour period.

FDA APPROVED INDICATION

Indicated as adjunctive therapy for the treatment of acute hyperammonemia due to deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS) from the time of birth. Also indicated as maintenance therapy for chronic hyperammonemia due to NAGS deficiency.

PRECAUTIONS

• Prolonged exposure to increased plasma ammonia levels can rapidly result in brain injury or death; monitoring recommended.
• During initial treatment, complete protein restriction is recommended for 24 to 48 hours; supplement calories to avoid catabolism and nitrogen turnover.

ADVERSE EFFECTS

Adverse reaction which occurred in 13% or more patients from a retrospective case series include abdominal pain, anemia, diarrhea, ear infection, headache, infection, nasopharyngitis, pyrexia, tonsillitis, and vomiting.

ADMINISTRATION

Do NOT administer tablets whole or crushed. Dissolve one 200-mg tablet in 2.5-mL of water for a concentration of 80 mg/mL for oral or nasogastric (NG) tube administration. For oral administration, measure dose using an oral syringe, discard the unused portion, administer immediately, then refill the oral syringe with 1 to 2 mL of water and administer immediately to ensure complete delivery of dose. For NG tube administration, measure dose using an oral syringe, discard the unused portion, administer immediately, and flush NG tube with small volume of water. Do not use other liquids or food for preparation or administration. Administer prior to feedings.

MONITORING

Monitor plasma ammonia levels, neurological status, and clinical response.