"Researchers from the National Institutes of Health have entered into an agreement with biotechnology company Vtesse, Inc., of Gaithersburg, Maryland, to develop treatments for Niemann-Pick disease type C (NPC) and other lysosomal storage disor"...
Any episode of acute symptomatic hyperammonemia should be treated as a life-threatening emergency. Treatment of hyperammonemia may require dialysis, preferably hemodialysis, to remove a large burden of ammonia. Uncontrolled hyperammonemia can rapidly result in brain injury/damage or death, and prompt use of all therapies necessary to reduce plasma ammonia levels is essential.
Management of hyperammonemia due to NAGS deficiency should be done in coordination with medical personnel experienced in metabolic disorders. Ongoing monitoring of plasma ammonia levels, neurological status, laboratory tests and clinical responses in patients receiving Carbaglu is crucial to assess patient response to treatment.
Plasma ammonia levels should be maintained within normal range for age via individual dose adjustment.
Since hyperammonemia is the result of protein catabolism, complete protein restriction is recommended to be maintained for 24 to 48 hours and caloric supplementation should be maximized to reverse catabolism and nitrogen turnover.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with carglumic acid.
There were no effects on fertility or reproductive performance in female rats at oral doses up to 2000 mg/kg/day (1.3 times the maximum recommended human starting dose based on body surface area). In a separate study, mating and fertility were unaffected in male rats at oral doses up to 1000 mg/kg/day (0.6 times the maximum recommended human starting dose based on body surface area).
Use In Specific Populations
Pregnancy Category C
There are no adequate and well controlled studies or available human data with Carbaglu® in pregnant women. Decreased survival and growth occurred in offspring born to animals that received carglumic acid at doses similar to the maximum recommended starting human dose during pregnancy and lactation. Because untreated N-acetylglutamate synthase (NAGS) deficiency results in irreversible neurologic damage and death, women with NAGS must remain on treatment throughout pregnancy. In embryo-fetal developmental toxicity studies, pregnant rats and rabbits received oral carglumic acid during organogenesis at doses up to 1.3 times the maximum recommended human starting dose based on body surface area (mg/m²). Actual doses were 500 and 2000 mg/kg/day (rats) and 250 and 1000 mg/kg/day (rabbits). The high doses resulted in maternal toxicity in both rats and rabbits. No effects on embryo-fetal development were observed in either species.
In a peri-and post-natal developmental study, female rats received oral carglumic acid from organogenesis through day 21 post-partum at doses up to 1.3 times the maximum recommended starting human dose based on body surface area (mg/m²). Actual doses were 500 and 2000 mg/kg/day. A reduction in offspring survival was seen at the high dose and a reduction in offspring growth was seen at both doses.
It is not known whether Carbaglu® is excreted in human milk. Carglumic acid is excreted in rat milk, and an increase in mortality and impairment of body weight gain occurred in neonatal rats nursed by mothers receiving carglumic acid. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Carbaglu®, human milk-feeding is not recommended. Treatment is continuous and life-long for NAGS deficiency patients.
The efficacy of Carbaglu for the treatment of hyperammonemia in patients with NAGS deficiency from birth to adulthood was evaluated in a retrospective review of the clinical course of 23 NAGS deficiency patients who all began Carbaglu treatment during infancy or childhood. There are no apparent differences in clinical response between adults and pediatric NAGS deficiency patients treated with Carbaglu, however, data are limited.
Carbaglu has not been studied in the geriatric population. Therefore, the safety and effectiveness in geriatric patients have not been established
Last reviewed on RxList: 8/16/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Carbaglu Information
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