Carglumic Acid

What it is and how it works

Mechanism of Action Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG) which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N‑acetylglutamate synthase (NAGS), a mitochondrial liver enzyme. NAG acts as the essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1), a mitochondrial liver enzyme which catalyzes the first reaction of the urea cycle. The urea cycle, whose role is the disposition of ammonia, includes a series of biochemical reactions in the liver resulting in the conversion of ammonia into urea, which is then excreted through the urine.

Mechanism class: Carbamoyl Phosphate Synthetase 1 Activators

Indications

1. INDICATIONS AND USAGE CARBAGLU is a carbamoyl phosphate synthetase 1 (CPS 1) activator indicated in pediatric and adult patients as: Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to N-acetylglutamate synthase (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 propionic acidemia (PA) or methylmalonic acidemia (MMA). Acute and Chronic Hyperammonemia due to N‑acetylglutamate Synthase (NAGS) Deficiency CARBAGLU is indicated in adult and pediatric patients as: 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. Acute Hyperammonemia due to Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA) CARBAGLU is indicated in adult and pediatric patients as adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to PA or MMA.

Dosage and administration (summary)

2. DOSAGE AND ADMINISTRATION Acute Hyperammonemia due to NAGS deficiency The recommended dosage in adult and pediatric patients is 100 mg/kg to 250 mg/kg orally daily. Divide the daily dosage into 2 to 4 doses. Chronic Hyperammonemia due to NAGS deficiency The recommended dosage in adult and pediatric patients is 10 mg/kg to 100 mg/kg orally daily. Divide the daily dosage into 2 to 4 doses. Therapeutic Monitoring for NAGS Deficiency Closely monitor plasma ammonia and titrate dosage to maintain the ammonia level within normal range for the patient's age, taking into consideration their clinical condition.

Contraindications

4. CONTRAINDICATIONS None None.

Pregnancy

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women with NAGS deficiency exposed to CARBAGLU. If CARBAGLU is administered during pregnancy, health care providers should report CARBAGLU exposure by calling 1-888-575-8344.

Storage and supply

16. HOW SUPPLIED/STORAGE AND HANDLING Ho w Supplied CARBAGLU is a white and elongated 200 mg tablet for oral suspension, functionally scored with 3 lines for splitting into 4 equal portions, and coded "C" on one side. CARBAGLU is supplied in a high-density polyethylene bottle with a child resistant polypropylene cap and desiccant unit.

Source: Carglumic Acid (Carbaglu) — US FDA prescribing information, 2024-01-25, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.