Carbaglu

What it is

Carbaglu is a dispersible tablet containing 200 mg of carglumic acid. Carglumic acid is a structural analogue of N-acetylglutamate (NAG), which is the naturally occurring activator of carbamoyl phosphate synthetase 1 (CPS 1), the first enzyme of the urea cycle.

Approved indications

Carbaglu is indicated in treatment of hyperammonaemia due to N-acetylglutamate synthase primary deficiency and hyperammonaemia due to Organic Acidaemias. — Hyperammonaemia due to N-acetylglutamate synthase primary deficiency — Hyperammonaemia due to isovaleric acidaemia — Hyperammonaemia due to methylmalonic acidaemia — Hyperammonaemia due to propionic acidaemia

Dosing overview

The recommended initial dose for acute hyperammonaemia is 100 mg/kg/day to 250 mg/kg/day for both adult and paediatric patients. Dosing should be titrated based on individual patient plasma ammonia levels and clinical symptoms, with the recommended maintenance dose titrated to target normal plasma ammonia level for age. The total daily dose should be divided into 2 to 4 doses and rounded to the nearest 100 mg. Patients with moderate renal impairment (GFR 30–59 mL/min) should receive an initial dose of 50 mg/kg/day to 125 mg/kg/day, with long-term daily doses in the range of 5 mg/kg/day to 50 mg/kg/day adjusted individually to maintain normal ammonia plasma levels. Patients with severe renal impairment (GFR ≤ 29 mL/min) should receive an initial dose of 15 mg/kg/day to 40 mg/kg/day, with long-term daily doses in the range of 2 mg/kg/day to 20 mg/kg/day adjusted individually to maintain normal ammonia plasma levels.

Key safety warnings

Any episode of acute symptomatic hyperammonaemia should be treated as a life-threatening emergency, as uncontrolled hyperammonaemia can rapidly result in brain injury or death. Due to a small dataset, any association between carglumic acid and cardiotoxicity or hepatotoxicity cannot be reliably determined; therefore, cardiac and hepatic function monitoring is advised during treatment. Ongoing monitoring of neurological and cardiac status, laboratory tests (renal, hepatic, haematological) and clinical responses in patients receiving carglumic acid is crucial to assess patient response.

Contraindications

Carbaglu is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Breast-feeding during the use of carglumic acid is contraindicated.

Regulatory history

The TGA approved Carbaglu (carglumic acid) for registration on 30 January 2015. ARTG registration 215632 for Carbaglu carglumic acid 200 mg dispersible tablets was first listed on 12 February 2015.