Carglumic acid

Source SPC is Carglumic Acid 200 mg Dispersible Tablets; treatment should be initiated under the supervision of a physician experienced in the treatment of metabolic disorders. Indication-specific regimens from §4.2: N-acetylglutamate synthase (NAGS) deficiency — initial daily dose 100 mg/kg, up to 250 mg/kg if necessary, then adjusted individually to maintain normal plasma ammonia; in the long term it may not be necessary to increase the dose with body weight provided metabolic control is adequate, with daily doses ranging from 10 mg/kg to 100 mg/kg. Isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia — start on hyperammonaemia; initial daily dose 100 mg/kg, up to 250 mg/kg if necessary, then adjusted individually. Responsiveness test before long-term treatment: in a comatose child start at 100–250 mg/kg/day measuring plasma ammonia at least before each administration (should normalise within a few hours); in moderate hyperammonaemia give a test dose of 100–200 mg/kg/day for 3 days at constant protein intake with repeated ammonia determinations. Plasma ammonia and amino acids should be maintained within normal limits; protein restriction and arginine supplementation may be indicated if protein tolerance is low. Contains up to 3 mg sodium per tablet — considered high in sodium (the maximum daily dose equals 20% of the WHO recommended maximum daily sodium intake).

Based on clinical experience, treatment may be started as early as the first day of life. Safety and effectiveness have been established in paediatric patients from birth to 17 years for acute or chronic hyperammonaemia due to NAGS deficiency and acute hyperammonaemia due to IVA, PA or MMA; posology adjustments in neonates are not deemed necessary. Dose is adjusted individually to maintain normal plasma ammonia levels. Extra care is needed with small doses — tablets can be halved and occasionally quartered to adjust the posology.