Carglumic acid
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From MedlinePlus, U.S. National Library of Medicine
Carbamoyl Phosphate Synthetase 1 Activator
Dosing in kidney impairment
Dosage Adjustment in Patients with Renal Impairment No dosage adjustment is warranted in patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m 2 ). The recommended dosage of CARBAGLU in patients with moderate or severe renal impairment is shown below. [See table below.] 25 mg/kg/day for patients weighing ≤ 15 kg 0.55 g/m 2 /day for patients weighting > 15 kg Divide daily dosage into 2 equal doses and round up to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet); administer each dose 12 hours apart.
| Moderate Renal Impairment (eGFR 30-59 mL/min/1.73 m2) | Severe Renal Impairment (eGFR 15-29 mL/min/1.73 m2) | |
|---|---|---|
| Acute Hyperammonemia due to NAGS Deficiency | 50 mg/kg/day to 125 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet) | 15 mg/kg/day to 60 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet) |
| Chronic Hyperammonemia due to NAGS Deficiency | 5 mg/kg/day to 50 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet) | 2 mg/kg/day to 25 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet) |
| Acute Hyperammonemia due to PA or MMA | 75 mg/kg/day for patients weighing ≤ 15 kg1.7 g/m2/day for patients weighting > 15 kgDivide daily dosage into 2 equal doses and round up to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet); administer each dose 12 hours apart. | 25 mg/kg/day for patients weighing ≤ 15 kg0.55 g/m2/day for patients weighting > 15 kgDivide daily dosage into 2 equal doses and round up to the nearest 50 mg (i.e., one-quarter of a CARBAGLU tablet); administer each dose 12 hours apart. |
Preparation and administration
Important Administration Instructions Disperse CARBAGLU tablets in water. Do not swallow whole or crush [see Dosage and Administration ] . CARBAGLU may be administered by mouth or via a nasogastric or gastrostomy tube [see Dosage and Administration ] .
Preparation and Administration Overview Disperse CARBAGLU tablets in water. Do not swallow whole or crush. CARBAGLU tablets do not dissolve completely in water, and undissolved particles of the tablet may remain in the mixing container. Take CARBAGLU immediately before meals or feedings. The CARBAGLU suspension has a slightly acidic taste.
For all preparations, use in foods or liquids other than water has not been studied and is not recommended. Oral Administration For oral administration, administer CARBAGLU as follows: Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose.
Add the CARBAGLU tablets to the water in the cup. Carefully stir the tablet and water mixture. Swallow the mixture immediately. Pieces of the tablet may remain in the cup. Rinse the cup with additional water and swallow the mixture immediately. Repeat as needed until no pieces of the tablet are left in the cup. U s e of an O r al Sy ri nge for Oral Administration For administration via an oral syringe, administer CARBAGLU as follows: Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose.
Add the CARBAGLU tablets to the water in the cup. Carefully stir the tablet and water mixture. Draw up the mixture in an oral syringe and administer immediately. Pieces of the tablet may remain in the oral syringe. Refill the oral syringe with a minimum volume of water (1 mL to 2 mL) and administer immediately. Flush the oral syringe again, as needed, until no pieces of the tablet are left in the syringe.
Use of Nasogastric Tube (NG Tube) or Gastrostomy Tube (G-Tube) for Feeding Tube Administration For patients who have a NG tube or G-tube in place, administer CARBAGLU as follows: Add a minimum of 2.5 mL of water into a small cup for each CARBAGLU tablet or each ½ or ¼ CARBAGLU tablet needed for the prescribed dose. Add the CARBAGLU tablets to the water in the cup.
Carefully stir the tablet and water mixture. Draw up the mixture into a catheter-tip syringe. Administer the mixture immediately through the NG tube or G-tube. Pieces of the tablet may remain in the catheter-tip syringe or the feeding tube. Flush immediately with 1 to 2 mL of additional water to clear the NG tube or G-tube.
Flush the NG tube or G-tube again, as needed, until no pieces of the tablet are left in the syringe or the feeding tube.
Contraindications
4. CONTRAINDICATIONS None None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women with NAGS deficiency exposed to CARBAGLU. If CARBAGLU is administered during pregnancy, health care providers should report CARBAGLU exposure by calling 1-888-575-8344. Risk Summary Although rare case reports of CARBAGLU use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, untreated NAGS deficiency, PA and MMA can result in irreversible neurologic damage and death in pregnant women (see Clinical Considerations ).
In an animal reproduction study, decreased survival and growth occurred in offspring born to rats that received carglumic acid at a dose approximately 38 times the maximum reported human maintenance dose. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnant women with urea cycle disorders, PA, and MMA may experience an increase in catabolic stress which can trigger a hyperammonemic crisis both in the intrapartum and in the post-partum (3-14 days post-partum) periods. Maternal complications related to hyperammonemic crisis can include neurological impairment, coma and in some cases death.
Data Animal Data No effects on embryo-fetal development were observed in pregnant rats treated with up to 2000 mg/kg/day (approximately 38 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC [area under the plasma concentration-time curve]) from two weeks prior to mating through organogenesis or in pregnant rabbits treated with up to 1000 mg/kg/day (approximately 6 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC) during organogenesis. In a pre- and post-natal developmental study, female rats received oral carglumic acid from organogenesis through lactation at doses of 500 mg/kg/day and 2000 mg/kg/day.
Decreased growth of offspring was observed at 500 mg/kg/day and higher (approximately 38 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC), and reduction in offspring survival during lactation was observed at 2000 mg/kg/day (approximately 38 times the…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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