Dosing and uses of Carbaglu (carglumic acid)
Adult dosage forms and strengths
dispersible tablet
- 200mg
Hyperammonemia
Initial dose range: 100-250 mg/kg/day PO/NG divided in 2-4 doses before meals; round total daily dose to nearest 100 mg
Maintenance: Generally <100 mg/kg/day in chronic hyperammonemia
Use of other ammonia-lowering therapies (eg, diet, hemodialysis) with carglumic acid during episodes of acute hyperammonemia is recommended
Administration
Disperse 200-mg dispersible tab in 2.5 mL water (resulting in 80 mg/mL) and administer immediately
Do not swallow whole or crush
Adjust dose according to ammonia levels and symptoms
Pediatric dosage forms and strengths
dispersible tablet
- 200mg
Hyperammonemia
Initial dose range: 100-250 mg/kg/day PO/NG divided in 2-4 doses before meals; round total daily dose to nearest 100 mg
Maintenance: Generally <100 mg/day in chronic hyperammonemia
Use of other ammonia-lowering therapies (eg, diet, hemodialysis) with carglumic acid during episodes of acute hyperammonemia is recommended
Other Information
Disperse 200-mg dispersible tab in 2.5 mL water (resulting in 80 mg/mL) and administer immediately
Do not swallow whole or crush
Adjust dose according to ammonia levels and symptoms
Carbaglu (carglumic acid) adverse (side) effects
Note: Adverse effects are derived from retrospective case series of 23 patients
>10%
Vomiting (26%)
Abdominal pain (17%)
Pyrexia (17%)
Tonsillitis (17%)
Anemia (13%)
Ear infection (13%)
Diarrhea (13%)
Nasopharyngitis (13%)
Headache (13%)
1-10%
Asthenia (9%)
Somnolence (9%)
Dysgeusia (9%)
Hyperhidrosis (9%)
Weakness (9%)
Pneumonia (9%)
Anorexia (9%)
Weight loss (9%)
Influenza (9%)
Rash (9%)
Warnings
Contraindications
None
Cautions
Monitor serum ammonia levels and adjust dose to maintain within normal range for age
Treat acute hyperammonemia episode as life-threatening emergency
During acute hyperammonemic episodes, protein restriction and hypercaloric intake recommended to block ammonia generating catabolic pathways; when normalized, protein intake can usually be increased with goal of unrestricted protein intake
Pregnancy and lactation
Pregnancy
Pregnancy category: C; no adequate, well controlled studies or available human data 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 NAGS deficiency results in irreversible neurologic damage and death, women with NAGS must remain on treatment throughout pregnancy
Lactation
Unknown whether distributed in human breast milk, breastfeeding not recommended
Excreted in rat milk, and increased 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, human breastfeeding is not recommended since treatment is continuous and life-long for NAGS deficiency patients
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Carbaglu (carglumic acid)
Mechanism of action
Structural analogue of N-acetylglutamate, which enters cells and enables activation of CPS I (first enzyme of urea cycle) in vivo; therefore, decreases hyperammonemia by converting ammonia into urea
Pharmacokinetics
Half-Life: 5.6 hr
Bioavailability: Absolute biovailability is not known
Vd: 2657 L
Peak Plasma Time: 3 hr (range: 2-4 hr)
Metabolism: portion metabolized by intestinal bacterial flora; likely end product is carbon dioxide eliminated via lungs
Clearance: 5.7 L/min (total); 290 mL/min (renal)
Excretion: unchanged in feces (60%) and urine (9%)
