CARGLUMIC ACID tablet, for suspension

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Eton Pharmaceuticals, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Carglumic acid tablets for oral suspension are 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. None Risk Summary Although rare case reports of Carglumic acid tablets for oral suspension 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 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 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 Carglumic acid tablets for oral suspension and any potential adverse effects on the breastfed child from Carglumic acid tablets for oral suspension or from the underlying maternal condition. The safety and effectiveness of Carglumic acid tablets for oral suspension for the treatment of pediatric patients (birth to 17 years of age) with acute or chronic hyperammonemia due to NAGS deficiency 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 Carglumic acid tablets for oral suspension. Clinical studies of Carglumic acid tablets for oral suspension 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 Carglumic acid tablets for oral suspension 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. Carglumic Acid Tablets for Oral Suspension Important information: - Carglumic acid tablets for oral suspension must be mixed in water before taking . Carglumic acid tablets for oral suspension should not be mixed in any other food or liquid. - Do not swallow Carglumic acid tablets for oral suspension whole. - Do not crush Carglumic acid tablets for oral suspension. - Take Carglumic acid tablets for oral suspension right before meals or feedings. - The Carglumic acid tablet for oral suspension and water mixture has a slightly sour taste. You may need to ask your healthcare provider or pharmacist for a medicine cup to measure the correct amount of water you will need to prepare the dose of Carglumic acid tablets for oral suspension. The Carglumic acid tablet for oral suspension tablet has 3 lines used for splitting the tablet into 4 equal parts in order to get the prescribed dose. Ask your healthcare provider if you have any questions about how to split the tablet the right way or have any questions about the prescribed dose. Taking Carglumic acid tablets for oral suspension by mouth using a cup: Children and Adults 1. Add a minimum of 2.5 mL of water into a small cup for each Carglumic acid tablet for oral suspension, or each ½ or ¼ Carglumic acid tablet for oral suspension, needed for the prescribed dose. For example: - If the prescribed dose is 2 Carglumic acid tablets for oral suspension, add a minimum of 5 mL of water into the cup. - If the prescribed dose is 2 and a ¼ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup.        - If the prescribed dose is 2 and a ½ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup. - Ask your healthcare provider if you are not sure of how much water you should use for the prescribed dose of Carglumic acid tablets for oral suspension. 2. Place the prescribed number of Carglumic acid tablets for oral suspension into the water in the cup. 3. Carefully stir the Carglumic acid tablet for oral suspension and water mixture in the cup to avoid spilling the mixture. Carglumic acid tablets for oral suspension do not dissolve completely in water. 4.Swallow the Carglumic acid tablets for oral suspension and water mixture right away . 5. Pieces of the tablet may remain in the cup. Add more water to the cup to rinse the cup and swallow the mixture right away . 6. Repeat step 5 until there are no pieces of the tablet left in the cup. Taking Carglumic acid tablets for oral suspension by mouth using an oral syringe: Children 1. Add a minimum of 2.5 mL of water into a small cup for each Carglumic acid tablet for oral suspension, or each ½ or ¼ Carglumic acid tablet for oral suspension, needed for the prescribed dose. For example: - If the prescribed dose is 2 Carglumic acid tablets for oral suspension, add a minimum of 5 mL of water into the cup.   - If the prescribed dose is 2 and a ¼ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup. - If the prescribed dose is 2 and a ½ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup. - Ask your healthcare provider if you are not sure of how much water you should use for the prescribed dose of Carglumic acid tablets for oral suspension. 2. Place the prescribed number of Carglumic acid tablets for oral suspension into the water in the cup. 3. Carefully stir the Carglumic acid tablets for oral suspension and water mixture in the cup to avoid spilling the mixture. Carglumic acid tablets for oral suspension do not dissolve completely in water. 4. Draw up all of the Carglumic acid tablets for oral suspension and water mixture in the cup into an oral syringe. 5. Give your child the Carglumic acid tablets for oral suspension and water mixture right away by placing the tip of the oral syringe along the inner cheek of their mouth, on either the right or left side. Slowly push all the way down on the plunger to give the medicine. 6. Pieces of the tablet may remain in the oral syringe. Refill the oral syringe with a minimum of 1 mL to 2 mL of water, and give your child the mixture right away . 7. Repeat step 6 until there are no pieces of the tablet left in the oral syringe. Giving Carglumic acid tablets for oral suspension through a nasogastric (NG) or gastrostomy tube (G-tube): Children and Adults 1.Add a minimum of 2.5 mL of water into a small cup for each Carglumic acid tablet for oral suspension, or each ½ or ¼ Carglumic acid tablet for oral suspension, needed for the prescribed dose. For example: - If the prescribed dose is 2 Carglumic acid tablets for oral suspension, add a minimum of 5 mL of water into the cup. - If the prescribed dose is 2 and a ¼ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup.       - If the prescribed dose is 2 and a ½ Carglumic acid tablets for oral suspension, add a minimum of 7.5 mL of water into the cup. - Ask your healthcare provider if you are not sure of how much water you should use for the prescribed dose of Carglumic acid tablets for oral suspension. 2. Place the prescribed number of Carglumic acid tablets for oral suspension into the water in the cup. 3. Carefully stir the Carglumic acid tablets for oral suspension and water mixture in the cup to avoid spilling the mixture. Carglumic acid tablets for oral suspension do not dissolve completely in water. 4. Draw up all of the Carglumic acid tablets for oral suspension and water mixture in the cup into a catheter-tip syringe. 5. Connect the catheter-tip syringe to the NG tube or G-tube. 6. Give the Carglumic acid tablet for oral suspension and water mixture through the NG tube or G-tube right away . 7. Pieces of the tablet may remain in the catheter-tip syringe or NG tube or G-tube. 8. Refill the catheter-tip syringe with 1 mL to 2 mL of water and flush the NG tube or G-tube right away . 9. Repeat step 8 until there are no pieces of the tablet left in the catheter-tip syringe or NG tube or G-tube. How should I store Carglumic acid tablets for oral suspension? - Before opening , store Carglumic acid tablets for oral suspension at 20° to 25°C (68° to 77°F) in the bottle it comes in. - After opening , store Carglumic acid tablets for oral suspension at room temperature between 20° to 25°C (68° to 77°F). Do not store Carglumic acid tablets for oral suspension in a refrigerator after opening.         Keep Carglumic acid tablets for oral suspension in a tightly closed bottle to protect the tablets from moisture.       Write the date the Carglumic acid tablets for oral suspension bottle is opened on the bottle label. Throw away any unused tablets after 90       days from first opening the bottle. - Do not use Carglumic acid tablets for oral suspension after the expiration date on the bottle. - Keep Carglumic acid tablets for oral suspension and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. All Trademarks are the property of their respective owners. Manufactured by: Novitium Pharma LLC 70 Lake Drive, East Windsor New Jersey 08520 Distributed by: Eton Pharmaceuticals, Inc. Deer Park, IL 60010 USA Issued:  01/2024 LB4191-04

Product summary:

How Supplied Carglumic Acid Tablet for Oral Suspension is supplied as a white to off-white elongated 200 mg tablet for oral suspension, functionally scored with 3 lines for splitting into 4 equal portions, and coded "120" on one side and ''N" on other side. Carglumic Acid Tablets for Oral Suspension are supplied in a high density polyethylene bottle with a child resistant cap and desiccant unit. Each bottle contains 60 tablets. Bottles of 60 tablets: NDC 71863-114-60 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] in the original unopened bottle. After first opening of the container:

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CARGLUMIC ACID- CARGLUMIC ACID TABLET, FOR SUSPENSION
ETON PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CARGLUMIC ACID
TABLETS FOR ORAL SUSPENSION SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION FOR
CARGLUMIC ACID TABLETS FOR ORAL SUSPENSION.
CARGLUMIC ACID TABLETS FOR ORAL SUSPENSION
INITIAL U.S. APPROVAL: 2010
INDICATIONS AND USAGE
Carglumic acid tablets for oral suspension is a carbamoyl phosphate
synthetase 1 (CPS 1) activator
indicated in pediatric and adult patients as: (1)
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)
DOSAGE AND ADMINISTRATION
Acute Hyperammonemia due to NAGS deficiency (2.2) (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) (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) (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.
Patients with Renal Impairment (2.4) (2)
See Full Prescribing Information for Instructions on Dosage
Adjustment.
Preparation and Administration (2.5) (2)
Disperse Carglumic acid tablets for oral suspension in water. Do not
swallow whole or crushed.
Take immediately before meals or feedings.
For additional instructions on preparation and administration orally
or through a nasogastric tube or
gastrostomy tube, see Full Prescribing Information.
DOSAGE FORMS AND STRENGTHS
Tablets for oral suspension: 200 mg, functionally scored. (3) (3)
CONTRAINDICATIONS
None. (4) (4)
ADVERSE REACTIO