Version May 2024
N-acetylglutamate synthase deficiency: Oral:
Acute hyperammonemia: 100 to 250 mg/kg/day given in 2 to 4 divided doses (rounded to the nearest 100 mg); titrate to age-appropriate plasma ammonia levels and clinical symptoms. Concomitant adjunctive ammonia-lowering therapy recommended.
Chronic hyperammonemia: 10 to 100 mg/kg/day given in 2 to 4 divided doses (rounded to the nearest 100 mg); titrate to age-appropriate normal plasma ammonia levels. Consider concomitant adjunctive ammonia-lowering therapy and protein restriction based on plasma ammonia levels.
Propionic acidemia or methylmalonic acidemia, acute hyperammonemia: Oral: 3.3 g/m2/day in 2 divided doses (12 hours apart); round dose up to the nearest 50 mg. Continue treatment until plasma ammonia level is <50 micromole/L and for a maximum of 7 days; concomitant adjunctive ammonia-lowering therapy recommended.
|
eGFR (mL/minute/1.73 m2) |
If the usual recommended dose is 10 to 100 mg/kg/ day in 2 to 4 divided doses |
If the usual recommended dose is 100 to 250 mg/kg/ day in 2 to 4 divided doses |
If the usual recommended dose is 3.3 g/m2/ day in 2 divided doses (12 hours apart) |
|---|---|---|---|
|
≥60 |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
|
30 to <60 |
5 to 50 mg/kg/day divided in 2 to 4 doses (round to nearest 50 mg) |
50 to 125 mg/kg/day in 2 to 4 divided doses (round to nearest 50 mg) |
1.7 g/m2/day divided in 2 equal doses administered every 12 hours (round to nearest 50 mg) |
|
<30 |
2 to 25 mg/kg/day divided in 2 to 4 doses (round to nearest 50 mg) |
15 to 60 mg/kg/day in 2 to 4 divided doses (round to nearest 50 mg) |
0.55 g/m2/day divided in 2 equal doses administered every 12 hours (round to nearest 50 mg) |
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
(For additional information see "Carglumic acid: Pediatric drug information")
N-acetylglutamate synthase (NAGS) deficiency:
Acute hyperammonemia, adjunct therapy: Infants, Children, and Adolescents: Oral: 100 to 250 mg/kg/day in 2 or 4 divided doses; round to the nearest 100 mg (ie, ½ Carbaglu tablet); titrate to age-appropriate plasma ammonia concentrations and clinical condition considerations (including nutritional requirements, protein intake, growth parameters, etc); concomitant ammonia-lowering therapy recommended.
Chronic hyperammonemia: Infants, Children, and Adolescents: Oral: Usual dose: 10 to 100 mg/kg/day in 2 or 4 divided doses; round to the nearest 100 mg (ie, ½ Carbaglu tablet); titrate to age-appropriate plasma ammonia concentrations and clinical condition considerations (including nutritional requirements, protein intake, growth parameters, etc). Rounding to the nearest 50 mg (ie, ¼ Carbaglu tablet) may be considered if a higher dose is not tolerated (Ref).
Propionic acidemia (PA) or methylmalonic acidemia (MMA), acute hyperammonemia, adjunctive therapy: Note: Administer concomitantly with other ammonia lowering therapies (eg, IV dextrose, insulin, L-carnitine, protein restriction, dialysis).
Infants, Children, and Adolescents:
≤15 kg: Oral: 150 mg/kg/day in divided doses every 12 hours. Round dose to the nearest 50 mg (ie, 1/4 Carbaglu tablet). Continue treatment until ammonia level is <50 micromol/L and for a maximum of 7 days (Ref). Dose range of 100 to 250 mg/kg/day in divided doses every 6 to 12 hours has been reported (Ref); some have suggested use of a loading dose of 100 mg/kg/dose (Ref).
>15 kg: Oral: 3.3 grams/m2/day in divided doses every 12 hours. Round dose to the nearest 50 mg (ie, 1/4 Carbaglu tablet). Continue treatment until ammonia level is <50 micromol/L and for a maximum of 7 days (Ref). Doses in the literature range from 100 to 250 mg/kg/day in divided doses every 6 to 12 hours (Ref); some have suggested use of a loading dose of 100 mg/kg/dose (Ref).
Neonates, Infants, Children, and Adolescents: Oral:
|
eGFR |
If the usual recommended dose is 10 to 100 mg/kg/day in 2 to 4 divided doses |
If the usual recommended dose is 100 to 250 mg/kg/day in 2 to 4 divided doses |
If the usual recommended dose is 150 mg/kg/day in 2 divided doses (12 hours apart) for PA or MMAa |
If the usual recommended dose is 3.3 g/m2/day in 2 divided doses (12 hours apart) |
|---|---|---|---|---|
|
a PA = propionic acidemia; MMA = methylmalonic acidemia. | ||||
|
b Round dose to nearest 50 mg (1/4 tablet). | ||||
|
≥60 mL/minute/1.73 m2 |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
|
30 to <60 mL/minute/1.73 m2 |
5 to 50 mg/kg/day divided in 2 to 4 dosesb |
50 to 125 mg/kg/day in 2 to 4 divided dosesb |
75 mg/kg/day in 2 equal doses administered every 12 hoursb |
1.7 g/m2/day divided in 2 equal doses administered every 12 hoursb |
|
<30 mL/minute/1.73 m2 |
2 to 25 mg/kg/day divided in 2 to 4 dosesb |
15 to 60 mg/kg/day in 2 to 4 divided dosesb |
25 mg/kg/day in 2 equal doses administered every 12 hoursb |
0.55 g/m2/day divided in 2 equal doses administered every 12 hoursb |
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain, diarrhea
Hematologic & oncologic: Anemia, neutropenia
Infection: Infection
Nervous system: Headache
Respiratory: Nasopharyngitis
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Cardiomyopathy
Dermatologic: Hyperhidrosis, skin rash
Endocrine & metabolic: Electrolyte disorder, hypoglycemia, weight loss
Gastrointestinal: Anorexia, decreased appetite, dysgeusia, increased serum lipase, pancreatitis, vomiting
Hematologic & oncologic: Leukocytosis
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Infection: Influenza
Nervous system: Behavioral problems, drowsiness, encephalopathy, lethargy, sleep disorder, stupor
Neuromuscular & skeletal: Asthenia
Respiratory: Apnea, hyperventilation, pneumonia
Postmarketing:
Dermatologic: Erythematous rash, maculopapular rash, pruritus, pustular rash
Nervous system: Mania
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to carglumic acid or any component of the formulation; breastfeeding.
Disease-related concerns:
• Kidney impairment: Plasma concentrations increased in patients with kidney impairment; dosage adjustment recommended.
Other warnings/precautions:
• Experienced physician: Acute symptomatic hyperammonemia is a life-threatening emergency; management of hyperammonemia due to N-acetylglutamate synthase deficiency should be done in coordination with those experienced in the management of metabolic disorders.
• Nutritional management: 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Soluble, Oral:
Carbaglu: 200 mg [scored]
Generic: 200 mg
Yes
Tablet,Dispersible (Carbaglu Oral)
200 mg (per each): $264.68
Tablet,Dispersible (Carglumic Acid Oral)
200 mg (per each): $218.44 - $251.45
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Soluble, Oral:
Carbaglu: 200 mg
Carbaglu is not available through pharmaceutical wholesalers or retail pharmacies, but only through direct shipping from the Accredo specialty pharmacy. Prescribers must contact Accredo Health Group at 888-454-8860 or refer to www.carbaglu.net to initiate patients on this product. For emergency (STAT) orders, call 877-900-9223.
Oral: Administer immediately prior to meals or feedings. Disperse in water prior to administration; should not be mixed with any other foods or liquids other than water.
Tablets: Do not swallow whole or crush. Disperse in water and administer immediately. Tablets do not dissolve completely, and some particles may remain; rinse container with water and administer rinse immediately; repeat as needed until no tablet pieces are left.
Oral syringe: After dispersion of tablets in water, draw up tablet and water mixture in oral syringe and administer immediately. After initial administration, pieces of tablet may remain in syringe; refill oral syringe with a minimum of 1 to 2 mL of water and administer immediately; repeat as needed until no pieces of tablet are left.
NG tube/G-tube: After dispersion of tablets in water, immediately administer through an NG tube or G-tube (tablets do not dissolve completely; some particles may remain). Flush immediately with 1 to 2 mL additional water to clear the tube; repeat as needed until no pieces of tablet are left in syringe or feeding tube.
Oral: Administer immediately before meals.
Tablets: Do not swallow whole or crush. Disperse in water and administer immediately. Tablets do not dissolve completely, and some particles may remain; rinse container with water and administer rinse immediately; repeat as needed until no tablet pieces are left. Carglumic acid tablets should not be mixed with any other foods or liquids other than water.
Oral syringe: After dispersion of tablets in water, draw up mixture into an oral syringe and administer immediately. After initial administration, pieces of tablet may remain in syringe; refill oral syringe with a minimum of 1 to 2 mL of water and administer immediately; repeat as needed until no pieces of tablet are left.
NG or gastrostomy tube: After dispersion of tablets in water, draw up mixture in a catheter-tip syringe and immediately administer through an NG or gastrostomy tube. After initial administration, pieces of tablet may remain in syringe or tube; flush immediately with 1 to 2 mL additional water to clear the tube; repeat as needed until no pieces of tablet are left in syringe or tube.
Hyperammonemia, N-acetylglutamate synthase deficiency: Adjunctive treatment of acute hyperammonemia and maintenance therapy of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase in adult and pediatric patients.
Hyperammonemia, propionic acidemia or methylmalonic acidemia : Adjunctive treatment of acute hyperammonemia due to propionic acidemia or methylmalonic acidemia in adult and pediatric patients.
Substrate of OAT1/3
There are no known significant interactions.
Untreated maternal N-acetylglutamate synthase deficiency can trigger a hyperammonemic crisis leading to neurological impairment, coma, and possibly death. Information specific to the use of carglumic acid in pregnancy has not been located (Wilcox 2018).
Data collection to monitor pregnancy and infant outcomes following exposure to carglumic acid is ongoing. Health care providers are encouraged to enroll patients exposed to carglumic acid during pregnancy in the pregnancy pharmacovigilance program (1-888-575-8344).
It is not known if carglumic acid is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Plasma ammonia concentrations; monitor for physical signs/symptoms of hyperammonemia (eg, lethargy, ataxia, confusion, vomiting, seizures, and memory impairment).
N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme which produces N-acetylglutamate (NAG). NAG is a required allosteric activator of the hepatic mitochondrial enzyme, carbamoyl phosphate synthetase 1, which converts ammonia into urea in the first step of the urea cycle. In NAGS-deficient patients, carglumic acid serves as a replacement for NAG.
Bioavailability: ~10%.
Metabolism: Via intestinal flora to carbon dioxide.
Half-life elimination: 25 hours.
Time to peak: Median: 3 hours (range: 2 to 4 hours).
Excretion: Feces (≤60% as unchanged drug); urine (9% as unchanged drug).
Kidney function impairment: The geometric mean ratio (90% CI) of AUC0-t in subjects with eGFR 60 to <90, eGFR 30 to <60, and eGFR ≤30 were approximately 1.3 (1.01, 1.68), 2 (1.65, 2.54), and 4.6 (3.36, 6.34), respectively, compared to subjects with normal kidney function.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
