1.2 Maintenance therapy for chronic hyperammonemia in patients with NAGS deficiency
1.2 Maintenance therapy for chronic hyperammonemia in patients with NAGS deficiency
Carbaglu® is indicated for maintenance therapy in pediatric and adult patients for chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be reduced or discontinued based on plasma ammonia levels.
Carbaglu® is indicated for maintenance therapy in pediatric and adult patients for chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be reduced or discontinued based on plasma ammonia levels.
Carbaglu treatment should be initiated by a physician experienced in metabolic disorders.
|offLabelAdultGuideSupport=
Adult Dosage and Administration
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
Recommended initial dose range for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. ( 2.1)
The recommended maintenance dose should be titrated to target normal plasma ammonia level for age. ( 2.1)
Divide the total daily dose into two to four doses to be given immediately before meals or feedings. ( 2.1)
Each divided dose should be rounded to the nearest 100 mg. ( 2.1)
Each 200 mg tablet should be dispersed in a minimum of 2.5 mL of water and taken immediately. ( 2.2)
Carbaglu can be administered orally or through a nasogastric tube. ( 2.3)
Carbaglu tablets should not be swallowed whole or crushed. ( 2.2)
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
|fdaLIADPed=Recommended initial dose range for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. ( 2.4)
The recommended maintenance dose should be titrated to target normal plasma ammonia levels for age. ( 2.4)
* Dosing Information
Divide the total daily dose into two to four doses to be given immediately before meals or feedings. ( 2.4)
Mix each 200 mg tablet in 2.5 mL of water to yield a concentration of 80 mg/mL. ( 2.5)
:* Dosage
Carbaglu may be administered orally with an oral syringe or through a nasogastric tube. ( 2.5, 2.6)
Carbaglu tablets should not be swallowed whole or crushed.( 2.2)
=====Condition2=====
|offLabelPedGuideSupport=
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
|offLabelPedNoGuideSupport=
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
<!--Contraindications-->
|contraindications=* Condition1
|warnings=* 5.1 Hyperammonemia
<!--Warnings-->
|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
Any episode of acute symptomatic hyperammonemia should be treated as a life-threatening emergency. Treatment of hyperammonemia may require dialysis, preferably hemodialysis, to remove a large burden of ammonia. Uncontrolled hyperammonemia can rapidly result in brain injury/damage or death, and prompt use of all therapies necessary to reduce plasma ammonia levels is essential.
=====Urogenital=====
Management of hyperammonemia due to NAGS deficiency should be done in coordination with medical personnel experienced in metabolic disorders. Ongoing monitoring of plasma ammonia levels, neurological status, laboratory tests and clinical responses in patients receiving Carbaglu is crucial to assess patient response to treatment.
5.2 Therapeutic Monitoring
Plasma ammonia levels should be maintained within normal range for age via individual dose adjustment.
5.3 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.
=====Miscellaneous=====
|clinicalTrials=6.1 Retrospective Case Series Experience
The most common adverse reactions (occurring in ≥ 13% of patients), regardless of causality, are: Infections, vomiting, abdominal pain, pyrexia, tonsilitis, anemia, ear infection, diarrhea, nasopharyngitis, and headache.
Table 1 summarizes adverse reactions occurring in 2 or more patients treated with Carbaglu in the retrospective case series. Because these reactions were reported retrospectively, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Table 1: Adverse Reactions Reported in > 2 Patients in the Retrospective Case Series treated with Carbaglu
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
1.1 Acute hyperammonemia in patients with NAGS deficiency
Carbaglu® is indicated as an adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). During acute hyperammonemic episodes concomitant administration of Carbaglu with other ammonia lowering therapies such as alternate pathway medications, hemodialysis, and dietary protein restriction are recommended.
1.2 Maintenance therapy for chronic hyperammonemia in patients with NAGS deficiency
Carbaglu® is indicated for maintenance therapy in pediatric and adult patients for chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be reduced or discontinued based on plasma ammonia levels.
Carbaglu treatment should be initiated by a physician experienced in metabolic disorders.
Adult Dosage and Administration
Recommended initial dose range for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. ( 2.1)
The recommended maintenance dose should be titrated to target normal plasma ammonia level for age. ( 2.1)
Divide the total daily dose into two to four doses to be given immediately before meals or feedings. ( 2.1)
Each divided dose should be rounded to the nearest 100 mg. ( 2.1)
Each 200 mg tablet should be dispersed in a minimum of 2.5 mL of water and taken immediately. ( 2.2)
Carbaglu can be administered orally or through a nasogastric tube. ( 2.3)
Carbaglu tablets should not be swallowed whole or crushed. ( 2.2)
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Carglumic acid in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Carglumic acid in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Recommended initial dose range for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. ( 2.4)
The recommended maintenance dose should be titrated to target normal plasma ammonia levels for age. ( 2.4)
Divide the total daily dose into two to four doses to be given immediately before meals or feedings. ( 2.4)
Mix each 200 mg tablet in 2.5 mL of water to yield a concentration of 80 mg/mL. ( 2.5)
Carbaglu may be administered orally with an oral syringe or through a nasogastric tube. ( 2.5, 2.6)
Carbaglu tablets should not be swallowed whole or crushed.( 2.2)
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Carglumic acid in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Carglumic acid in pediatric patients.
Contraindications
There is limited information regarding Carglumic acid Contraindications in the drug label.
Warnings
5.1 Hyperammonemia
Any episode of acute symptomatic hyperammonemia should be treated as a life-threatening emergency. Treatment of hyperammonemia may require dialysis, preferably hemodialysis, to remove a large burden of ammonia. Uncontrolled hyperammonemia can rapidly result in brain injury/damage or death, and prompt use of all therapies necessary to reduce plasma ammonia levels is essential.
Management of hyperammonemia due to NAGS deficiency should be done in coordination with medical personnel experienced in metabolic disorders. Ongoing monitoring of plasma ammonia levels, neurological status, laboratory tests and clinical responses in patients receiving Carbaglu is crucial to assess patient response to treatment.
5.2 Therapeutic Monitoring
Plasma ammonia levels should be maintained within normal range for age via individual dose adjustment.
5.3 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.
Adverse Reactions
Clinical Trials Experience
6.1 Retrospective Case Series Experience
The most common adverse reactions (occurring in ≥ 13% of patients), regardless of causality, are: Infections, vomiting, abdominal pain, pyrexia, tonsilitis, anemia, ear infection, diarrhea, nasopharyngitis, and headache.
Table 1 summarizes adverse reactions occurring in 2 or more patients treated with Carbaglu in the retrospective case series. Because these reactions were reported retrospectively, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Table 1: Adverse Reactions Reported in > 2 Patients in the Retrospective Case Series treated with Carbaglu
