CARBAGLU- carglumic acid tablet, for suspension

Land: Verenigde Staten

Taal: Engels

Bron: NLM (National Library of Medicine)

Werkstoffen:

CARGLUMIC ACID (UNII: 5L0HB4V1EW) (CARGLUMIC ACID - UNII:5L0HB4V1EW)

Beschikbaar vanaf:

Recordati Rare Diseases

Toedieningsweg:

ORAL

Prescription-type:

PRESCRIPTION DRUG

therapeutische indicaties:

CARBAGLU is indicated in adult and pediatric patients as: - Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to NAGS deficiency. - Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency. CARBAGLU is indicated in adult and pediatric patients as adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to PA or MMA. None 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 maximum reported human maintenance dose [100 mg/kg/day] based on AUC). No effects on physical and sexual development, learning and memory, or reproductive performance were observed through maturation of the surviving offspring at maternal doses up to 2000 mg/kg/day. The high dose (2000 mg/kg/day) produced maternal toxicity (impaired weight gain and approximately 10% mortality). Risk Summary It is not known whether carglumic acid is present in human milk. There are no available data on the effects of carglumic acid on the breastfed infant or the effects on milk production. Carglumic acid is present in milk from treated rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CARBAGLU and any potential adverse effects on the breastfed child from CARBAGLU or from the underlying maternal condition. The safety and effectiveness of CARBAGLU for the treatment of pediatric patients (birth to 17 years of age) with acute or chronic hyperammonemia due to NAGS deficiency and acute hyperammonemia due to PA or MMA have been established, and the information on these uses are discussed throughout the labeling. There are insufficient data to determine if there is a difference in clinical or biochemical responses between adult and pediatric patients treated with CARBAGLU. Clinical studies of CARBAGLU did not include patients 65 years of age and older to determine whether they respond differently from younger patients. Plasma concentrations of carglumic acid increased in patients with renal impairment [see Clinical Pharmacology (12.3)] . Reduce the CARBAGLU dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.4)]. The pharmacokinetics of carglumic acid have not been evaluated in patients with end stage renal disease.

Product samenvatting:

Ho w Supplied CARBAGLU is a white and elongated 200 mg tablet for oral suspension, functionally scored with 3 lines for splitting into 4 equal portions, and coded "C" on one side. CARBAGLU is supplied in a high-density polyethylene bottle with a child resistant polypropylene cap and desiccant unit. Each bottle contains either 5 or 60 tablets. Bottle of 5 tablets: NDC 52276-312-05 Bottle of 60 tablets: NDC 52276-312-60 S t o r ag e Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original unopened bottle. After first opening of the bottle:

Autorisatie-status:

New Drug Application

Productkenmerken

CARBAGLU- CARGLUMIC ACID TABLET, FOR SUSPENSION
RECORDATI RARE DISEASES
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CARBAGLU SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CARBAGLU.
CARBAGLU (CARGLUMIC ACID) TABLETS FOR ORAL SUSPENSION
INITIAL U.S. APPROVAL: 2010
INDICATIONS AND USAGE
CARBAGLU is a carbamoyl phosphate synthetase 1 (CPS 1) activator
indicated in pediatric and adult
patients as:
Adjunctive therapy to standard of care for the treatment of acute
hyperammonemia due to N-
acetylglutamate synthase (NAGS) deficiency. (1.1)
Maintenance therapy for the treatment of chronic hyperammonemia due to
NAGS deficiency. (1.1)
Adjunctive therapy to standard of care for the treatment of acute
hyperammonemia due to propionic
acidemia (PA) or methylmalonic acidemia (MMA). (1.2)
DOSAGE AND ADMINISTRATION
Acute Hyperammonemia due to NAGS deficiency (2.2)
The recommended dosage in adult and pediatric patients is 100 mg/kg to
250 mg/kg orally daily. Divide
the daily dosage into 2 to 4 doses.
Chronic Hyperammonemia due to NAGS deficiency (2.2)
The recommended dosage in adult and pediatric patients is 10 mg/kg to
100 mg/kg orally daily. Divide
the daily dosage into 2 to 4 doses.
Therapeutic Monitoring for NAGS Deficiency (2.2)
Closely monitor plasma ammonia and titrate dosage to maintain the
ammonia level within normal
range for the patient's age, taking into consideration their clinical
condition.
Acute Hyperammonemia due to PA or MMA (2.3)
The recommended dosage in adult and pediatric patients is:
150 mg/kg orally daily for patients less than or equal to 15 kg
3.3 g/m orally daily for patients greater than 15 kg
Divide the daily dosage into 2 doses.
Continue treatment until ammonia level is less than 50 micromol/L and
for a maximum duration of 7
days.
Patients with Renal Impairment (2.4)
See Full Prescribing Information for Instructions on Dosage
Adjustment.
Preparation and Administration (2.5)
Disperse CARBAGLU tablets in water. Do not sw