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Carbaglu Carglumic Acid 200 mg Tablet, For Suspension, 5-count — NDC 52276-0312-05 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Carbaglu Carglumic Acid 200 mg Tablet, For Suspension, 5-count — NDC 52276-312-05 (Billing 52276-0312-05)

by Recordati Rare Diseases · 5 TABLET, FOR SUSPENSION in 1 BOTTLE

This is a package of 5 tablets of Carbaglu Carglumic Acid 200 mg Tablet, For Suspension from Recordati Rare Diseases, marketed since Mar 2010 and currently FDA-listed.

NDC 52276-0312-05
🏷️ FDA NDC (as labeled) 52276-312-05 billing pads the product segment with a zero
This package
Contains5-count Pack sizes2 compare ↓
Also priced by: Part D plans $376.88/unit — full pricing hub ↓
Product page 52276-0312-60 Also comes in: 60 tablets 52276-312-60
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 52276-312-05 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
52276 labeler · 312 product · 05 package
Package marketed since
Mar 18, 2010
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
5 EA per package
Barcode (UPC-A, from the NDC)
3 5227631205 0
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 52276-312-05
Product NDC 52276-312
11-digit billing NDC 52276031205
NCPDP billing unit EA — each (per item)
RxCUI 905390, 905394
UNII 5L0HB4V1EW
Application # NDA022562
SPL Set ID 10175e73-5172-4dde-a508-8a88b7afc0a1
Established class (EPC) Carbamoyl Phosphate Synthetase 1 Activator
Mechanism of action Carbamoyl Phosphate Synthetase 1 Activators
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2010-03-18
Route ORAL
Dosage form TABLET, FOR SUSPENSION
Substance CARGLUMIC ACID
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 30908230007320
GPI class Carbaglu
GCN Seq No 053150
GCN 20522
HICL code 025643
Ingredient (HICL) Carglumic Acid
HIC1 code D
Therapeutic class — broad (HIC1) Biliary System/Gastro-Intestinal System
HIC2 code D9
Therapeutic class — intermediate (HIC2) Ammonia Inhibitors
HIC3 code D9A
Therapeutic class — specific (HIC3) Ammonia Inhibitors
AHFS code 40:10.00.00
AHFS class Ammonia Detoxicants
FDB label name CARBAGLU 200 MG TAB FOR SUSP
FDB brand name Carbaglu
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 053150
  • GCN: 20522
  • GPI-14 (Medi-Span): 30908230007320
  • HICL (First Databank): 025643
  • AHFS class code: 40:10.00.00
  • RxCUI (RxNorm): 905390
Why two NDCs? The FDA registers this code as 52276-312-05 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 52276-0312-05. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Carbamoyl Phosphate Synthetase 1 Activator class.

Pharmacologic class Carbamoyl Phosphate Synthetase 1 Activator
Drug family (ATC) Amino acids and derivatives
How it works Carbamoyl Phosphate Synthetase 1 Activators
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name CARBAGLU 200 MG TAB FOR SUSP Ingredient Carglumic Acid

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $376.88 —
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
52276-0312-05 You're viewing this 5 TABLET, FOR SUSPENSION in 1 BOTTLE 2010-03-18 — Active
52276-0312-60 52276-312-60 Main listing 60 TABLET, FOR SUSPENSION in 1 BOTTLE 2010-03-18 — Active

You're viewing the smallest of 2 pack sizes for this product.

This pack shows little to no recent Medicaid volume — the 60 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 5-count package — 5 tablet, for suspension in 1 bottle.
How does this package differ from NDC 52276-0312-60?
Both are Carbaglu Carglumic Acid 200 mg Tablet, For Suspension — the drug itself is identical. This page's package is the 5-count one, while NDC 52276-0312-60 is the 60 tablets package.
What NDC number is used to bill for this package of Carbaglu Carglumic Acid 200 mg Tablet, For Suspension?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Carglumic acid 200 mg 35573-0459-60 Burel 60 tablets — AB FDA listed —
Carbaglu 200 mgthis 52276-0312-05 Recordati 5 tablets — AB FDA listed —
Carglumic acid 200 mg 68475-0006-01 Navinta 5 tablets — AB FDA listed —
Carglumic Acid 200 mg 71863-0114-60 Eton 60 tablets — AB FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2010
First FDA approval
Mar 2010
📍
2026
Currently FDA-listed
16 years listed
🛡️
2028
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2028. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Mar 18, 2010 AB TE-rated RLD RS ⏳ ~1.3 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
Exclusivity ODE-345
2010 2012 2014 2016 2018 2020 2022 2024 2026 2028
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

FDA exclusivity
CodeWhat it grantsExpires
ODE-345Orphan Drug Exclusivity (7-year)Jan 22, 2028
Common questions
Is there a generic version of CARBAGLU 200 MG TAB FOR SUSP?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for CARBAGLU 200 MG TAB FOR SUSP. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII 7CV7WJK4UI
    Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.

6 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerRecordati Rare Diseases
Application holderRECORDATI RARE DISEASES INC
FDA applicationNDA022562 (NDA)
Labeler code52276
First marketedMar 2010
Product typeHuman Prescription Drug
Portfolio2 products on file

More NDCs from Recordati Rare Diseases labeler code 52276

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 167 words ▾

1. 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 )

1.1Acute and Chronic Hyperammonemia due to N‑acetylglutamate Synthase (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 NAGS deficiency. Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.

1.2Acute Hyperammonemia due to Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA) 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.

⏱️ Dosage and Administration ~3 min read ▾

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 2 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 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.

2.1Important Administration Instructions Disperse CARBAGLU tablets in water. Do not swallow whole or crush [see Dosage and Administration (2.5) ] . CARBAGLU may be administered by mouth or via a nasogastric or gastrostomy tube [see Dosage and Administration (2.5) ] .

2.2Recommended Dosage for Acute or Chronic Hyperammonemia due to NAGS Deficiency Treatment Initiation Initiate CARBAGLU treatment as soon as the diagnosis of NAGS deficiency is suspected, which may be as soon as at birth, and supervised by a healthcare provider experienced in the treatment of metabolic disorders. Dosage for Acute Hyperammonemia due to NAGS Deficiency The recommended dosage of CARBAGLU in adult and pediatric patients for acute hyperammonemia due to NAGS deficiency is (based on actual body weight) 100 mg/kg to 250 mg/kg orally daily.

Divide the daily dosage into 2 to 4 doses and round to the nearest 100 mg (i.e., half of a CARBAGLU tablet). During acute hyperammonemic episodes, administer CARBAGLU with other ammonia lowering therapies, such as alternate pathway medications, hemodialysis, and protein restriction. Dosage for Chronic Hyperammonemia due to NAGS Deficiency The recommended dosage of CARBAGLU in adult and pediatric patients for chronic hyperammonemia due to NAGS deficiency is (based on actual body weight) 10 mg/kg to 100 mg/kg orally daily.

Divide the daily dosage into 2 to 4 doses and round to the nearest 100 mg (i.e., half of a CARBAGLU tablet). During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be needed based on plasma ammonia levels. Therapeutic Monitoring Closely monitor plasma ammonia levels.

Titrate the CARBAGLU dosage to maintain the plasma ammonia level within the normal range for the patient's age, taking into consideration their clinical condition (e.g., nutritional requirements, protein intake, growth parameters, etc.). Adjust the recommended dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.4) ] .

2.3Recommended Dosage for Acute Hyperammonemia due to PA or MMA Treatment Initiation Initiate CARBAGLU for the treatment of acute hyperammonemia in patients with a suspected or confirmed diagnosis of PA or MMA. Dosage for Acute Hyperammonemia due to PA or MMA The recommended dosage of CARBAGLU in adult and pediatric patients with acute hyperammonemia due to PA or MMA is (based on actual body weight): 150 mg/kg orally daily for patients less than or equal to 15 kg 3.3 g/m 2 orally daily for patients greater than 15 kg Divide the daily do… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 44 words ▾

3. DOSAGE FORMS AND STRENGTHS Tablets for oral suspension: 200 mg of carglumic acid, white, elongated, functionally scored with 3 lines (for splitting into 4 equal portions) and printed "C" on one side. Tablets for oral suspension: 200 mg, functionally scored. ( 3 )

⛔ Contraindications 7 words ▾

4. CONTRAINDICATIONS None None. ( 4 )

🤒 Adverse Reactions ~3 min read ▾

6. ADVERSE REACTIONS NAGS deficiency : Most common adverse reactions (≥13%) are vomiting, abdominal pain, pyrexia, tonsillitis, anemia, diarrhea, ear infection, infections, nasopharyngitis, hemoglobin decreased, and headache. ( 6.1 ) PA and MMA : Most common adverse reactions (≥5%) are neutropenia, anemia, vomiting, electrolyte imbalance, decreased appetite, hypoglycemia, lethargy/stupor, encephalopathy and pancreatitis/lipase increased.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Acute and Chronic Hyperammonemia due to NAGS Deficiency In a retrospective case series of 23 NAGS deficiency patients treated with CARBAGLU, 17 of the 23 patients reported an adverse reaction. The most common adverse reactions (occurring in ≥ 13% of patients) were vomiting, abdominal pain, pyrexia, tonsillitis, anemia, diarrhea, ear infection, infections, nasopharyngitis, hemoglobin decreased, and headache.

Table 1 summarizes adverse reactions occurring in 2 or more patients treated with CARBAGLU. Table 1: Adverse Reactions Reported in ≥ 2 Patients with NAGS deficiency Treated with CARBAGLU in the Retrospective Case Series Adverse Reaction Number of Patients (N) (%) Vomiting 6 (26) Abdominal pain 4 (17) Pyrexia 4 (17) Tonsillitis 4 (17) Anemia 3 (13) Diarrhea 3 (13) Ear infection 3 (13) Infections 3 (13) Nasopharyngitis 3 (13) Hemoglobin decreased 3 (13) Headache 3 (13) Dysgeusia 2 (9) Asthenia 2 (9) Hyperhidrosis 2 (9) Influenza 2 (9) Pneumonia 2 (9) Weight decreased 2 (9) Anorexia 2 (9) Somnolence 2 (9) Rash 2 (9) Acute Hyperammonemia due to PA and MMA In a randomized, double-blind, placebo-controlled clinical trial, 24 patients (15 with PA and 9 with MMA) experienced a total of 90 hyperammonemic episodes which were randomized 1:1 to be treated with either CARBAGLU or placebo, each in addition to standard-of-care therapy, with randomization based on each hyperammonemic episode.

The average patient age (SD) was 9.2 years (7.7) and 12 (50 %) were males. CARBAGLU was administered at a dosage of 150 mg/kg/day for patients ≤15 kg or 3.3 g/m 2 /day for patients >15 kg, divided into 2 doses, for a median duration of 4.14 days. At least 1 adverse reaction was reported during the course of hyperammonemic episodes in 42% of hyperammonemic episodes.

The most common adverse reactions (≥5%) during hyperammonemic episodes were neutropenia, anemia, vomiting, electrolyte imbalance, decreased appetite, hypoglycemia, lethargy/stupor, encephalopathy and pancreatitis/lipase increased. Table 2 summarizes adverse reactions (≥2%) during hyperammonemic episodes in patients with PA or MMA treated with CARBAGLU or placebo. Table 2: Adverse Reactions (≥ 2%) During Hyperammonemic Episodes in Patients with PA or MMA Treated with CARBAGLU or Placebo Adverse Reaction Treatment Arm CARBAGLU N=42 episodes PLACEBO N=48 episodes N (%) N (%) Neutropenia 6 (14) 4 (8) Anemia 5 (12) 4 (8) Vomiting 3 (7) 1 (2) Electrolyte imbalance 3 (7) 2 (4) Decreased appetite 2 (5) 1 (2) Hypoglycemia 2 (5) 1 (2) Lethargy/Stupor 2 (5) 1 (2) Encephalopathy 2 (5) 0 (0) Pancreatitis/Lipase increased 2 (5) 0 (0) Cardiomyopathy 1 (2) 0 (0) Alanine aminotransferase increased 1 (2) 0 (0) Aspartate aminotransferase increased 1 (2) 0 (0) Infusion site extravasation 1 (2) 0 (0) White blood cell count increased 1 (2) 0 (0) Behavior disorder 1 (2) 0 (0) Sleep disorder 1 (2) 0 (0) Apnea 1 (2) 0 (0) Hyperventilation 1 (2) 0 (0)

6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of CARBAGLU. Because these reactions are reported voluntarily from a population of uncert… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8. USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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).

8.2Lactation 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.

8.4Pediatric Use 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 differen… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy 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).

🧒 Pediatric Use 76 words ▾

8.4Pediatric Use 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.

🧓 Geriatric Use 26 words ▾

8.5Geriatric Use Clinical studies of CARBAGLU did not include patients 65 years of age and older to determine whether they respond differently from younger patients.

🆘 Overdosage 39 words ▾

10. OVERDOSAGE One patient treated with 650 mg/kg/day of CARBAGLU developed symptoms resembling monosodium glutamate intoxication-like syndrome and characterized by tachycardia, profuse sweating, increased bronchial secretions, increased body temperature, and restlessness. These symptoms resolved upon reduction of the dose.

🧬 Clinical Pharmacology ~3 min read ▾

12. CLINICAL PHARMACOLOGY

12.1Mechanism of Action Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG) which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N‑acetylglutamate synthase (NAGS), a mitochondrial liver enzyme. NAG acts as the essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1), a mitochondrial liver enzyme which catalyzes the first reaction of the urea cycle. The urea cycle, whose role is the disposition of ammonia, includes a series of biochemical reactions in the liver resulting in the conversion of ammonia into urea, which is then excreted through the urine.

Carglumic acid acts as a CPS1 activator, improves or restores the function of the urea cycle, and facilitates ammonia detoxification and urea production.

12.2Pharmacodynamics In a retrospective review of the clinical course in 23 patients with NAGS deficiency, carglumic acid reduced plasma ammonia levels within 24 hours when administered with and without concomitant ammonia lowering therapies. No dose-response relationship has been identified. Cardiac Electrophysiology The effect of carglumic acid was evaluated in a Phase 1, randomized study in 76 healthy volunteers.

The study suggests a lack of clinically relevant QT prolongation effect at the highest therapeutic dose level (250 mg/kg/day).

12.3Pharmacokinetics The pharmacokinetics of carglumic acid in healthy subjects following an intravenous (IV) infusion over 2 hours at 8 mg/kg or an oral administration at 100 mg/kg are summarized in Table 3 . Table 3: Mean (SD) Pharmacokinetic Parameter Values of Carglumic Acid in Healthy Subjects # Median (range); N/A, not applicable PK parameter IV infusion 8 mg/kg (N=10) Oral 100 mg/kg (N=12) C max (ng/mL) 8613 (558) 3284 (321) T max (hr) # 2 (1-2) 3 (2-4) AUC (ng*hr/mL) 24501 (1613) 31426 (2150) T ½ (hr) 31 (3) 25 (2) CL (L/hr/kg) 0.34 (0.02) N/A Vd (L/kg) 15 (1) N/A Abso r p ti o n Following an oral administration of CARBAGLU 100 mg/kg in healthy subjects, the absolute bioavailability was approximately 10%.

Distribution Carglumic acid is not bound to plasma proteins. Elimination Carglumic acid is predominantly excreted by the kidneys as unchanged product. M e t abo li s m A proportion of carglumic acid may be metabolized by the intestinal bacterial flora.

The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs. Excretion Following an oral administration of radiolabeled CARBAGLU at 100 mg/kg, 9% of the dose is excreted unchanged in the urine and up to 60% of the dose is recovered unchanged in the feces. Specific Populations Patients with Renal Impairment The pharmacokinetics of carglumic acid in subjects with renal impairment were compared with healthy subjects with normal renal function following oral administration of a single dose of CARBAGLU 40 mg/kg or 80 mg/kg.

The C max and AUC 0-t of carglumic acid are summarized in Table 4. The geometric mean ratio (90% CI) of C max in subjects with mild, moderate, and severe renal impairment relative to those in their matched control subjects with normal renal function were approximately 1.3 (0.95, 1.86), 2.0 (1.62, 2.50), and 4.4 (3.11, 6.28), respectively. The geometric mean ratio (90% CI) of AUC 0-t in subjects with mild, moderate, and severe renal impairment relative to those in their matched control subjects with normal renal function were approximately 1.4 (1.09, 1.73), 2.8 (2.27, 3.47), and 6.9 (5.21, 9.24), respectively [see Dosage and Administration (2.4) ] .

Table 4: Mean (SD) C max and AUC 0-t of Carglumic Acid Following Single Oral Dose Administration of CARBAGLU 80 mg/kg or 40 mg/kg in Subjects with Renal Impairment and Matched Healthy Control Subjects with Normal Renal Function PK Parameters Normal Renal Function 1a : eGFR ≥90 mL/min/1.73m 2 (N=8) Mild Renal Impairment: eGFR 60-89 mL/min/1.73m 2 (N=8) Moderate Renal Impairment: eGFR 30-59 mL/min/1.73m 2 (N=8) Normal Renal Function 1b : eGFR ≥90 m… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 117 words ▾

12.1Mechanism of Action Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG) which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N‑acetylglutamate synthase (NAGS), a mitochondrial liver enzyme. NAG acts as the essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1), a mitochondrial liver enzyme which catalyzes the first reaction of the urea cycle. The urea cycle, whose role is the disposition of ammonia, includes a series of biochemical reactions in the liver resulting in the conversion of ammonia into urea, which is then excreted through the urine.

Carglumic acid acts as a CPS1 activator, improves or restores the function of the urea cycle, and facilitates ammonia detoxification and urea production.

📦 How Supplied / Storage and Handling 154 words ▾

16. HOW SUPPLIED/STORAGE AND HANDLING 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: Store at room temperature between 15°C and 30°C (59°F and 86°F).

Do not refrigerate. Keep the bottle tightly closed between openings in order to protect from moisture. Write the date of opening on the bottle.

Do not use CARBAGLU after the expiration date stated on the bottle. Discard bottle one month after first opening.

📋 Description 102 words ▾

11. DESCRIPTION CARBAGLU tablets for oral suspension contain 200 mg of carglumic acid. Carglumic acid, the active substance, is a carbamoyl phosphate synthetase 1 (CPS 1) activator and is soluble in boiling water, slightly soluble in cold water, and practically insoluble in organic solvents.

The chemical name of carglumic acid is N-carbamoyl-L-glutamic acid or (2S)-2-(carbamoylamino) pentanedioic acid. The empirical formula is C 6 H 10 N 2 O 5 and the molecular weight is 190.16. The structural formula is: The inactive ingredients of CARBAGLU are croscarmellose sodium, hypromellose, microcrystalline cellulose, silica colloidal anhydrous, sodium lauryl sulfate, and sodium stearyl fumarate.

Carbaglu structure

💬 Information for Patients ~1 min read ▾

17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Instructions for Use ). Advise the patient or caregiver on the following: Preparation and Administration [see Dosage and Administration ( 2.5 )] Disperse CARBAGLU tablets in water.

Do not swallow whole or crushed. Take CARBABLU immediately before meals or feedings. CARBAGLU tablets dispersed in water can be administered orally or via a nasogastric tube or gastrostomy tube as described in the Instructions for Use .

Storage [see How Supplied/Storage and Handling ( 16 )] Store UNOPENED bottle in a refrigerator at 2°C to 8°C (36°F to 46°F). After first opening of the bottle: do not refrigerate, store at room temperature between 15°C and 30°C (59°F and 86°F). Keep the bottle tightly closed in order to protect from moisture.

Write the date of opening on the bottle. Discard bottle one month after first opening. Do not use CARBAGLU after the expiration date stated on the bottle.

Pregnancy [see Use in Specific Populations ( 8.1 )] Advise women with NAGS deficiency who are exposed to CARBAGLU during pregnancy that there is a pregnancy surveillance program that monitors pregnancy outcomes. This product's labeling may have been updated. For the most recent Prescribing Information, please visit www.recordatirarediseases.com/us or www.carbaglu.com.

Supplied by: Recordati Rare Diseases Puteaux, France Licensed to and Distributed by: Recordati Rare Diseases Inc. Bridgewater, NJ 08807 Carbaglu ® is a licensed trademark of Recordati Rare Diseases Inc. RRD logo

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetics of carglumic acid in healthy subjects following an intravenous (IV) infusion over 2 hours at 8 mg/kg or an oral administration at 100 mg/kg are summarized in Table 3 . Table 3: Mean (SD) Pharmacokinetic Parameter Values of Carglumic Acid in Healthy Subjects # Median (range); N/A, not applicable PK parameter IV infusion 8 mg/kg (N=10) Oral 100 mg/kg (N=12) C max (ng/mL) 8613 (558) 3284 (321) T max (hr) # 2 (1-2) 3 (2-4) AUC (ng*hr/mL) 24501 (1613) 31426 (2150) T ½ (hr) 31 (3) 25 (2) CL (L/hr/kg) 0.34 (0.02) N/A Vd (L/kg) 15 (1) N/A Abso r p ti o n Following an oral administration of CARBAGLU 100 mg/kg in healthy subjects, the absolute bioavailability was approximately 10%.

Distribution Carglumic acid is not bound to plasma proteins. Elimination Carglumic acid is predominantly excreted by the kidneys as unchanged product. M e t abo li s m A proportion of carglumic acid may be metabolized by the intestinal bacterial flora.

The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs. Excretion Following an oral administration of radiolabeled CARBAGLU at 100 mg/kg, 9% of the dose is excreted unchanged in the urine and up to 60% of the dose is recovered unchanged in the feces. Specific Populations Patients with Renal Impairment The pharmacokinetics of carglumic acid in subjects with renal impairment were compared with healthy subjects with normal renal function following oral administration of a single dose of CARBAGLU 40 mg/kg or 80 mg/kg.

The C max and AUC 0-t of carglumic acid are summarized in Table 4. The geometric mean ratio (90% CI) of C max in subjects with mild, moderate, and severe renal impairment relative to those in their matched control subjects with normal renal function were approximately 1.3 (0.95, 1.86), 2.0 (1.62, 2.50), and 4.4 (3.11, 6.28), respectively. The geometric mean ratio (90% CI) of AUC 0-t in subjects with mild, moderate, and severe renal impairment relative to those in their matched control subjects with normal renal function were approximately 1.4 (1.09, 1.73), 2.8 (2.27, 3.47), and 6.9 (5.21, 9.24), respectively [see Dosage and Administration (2.4) ] .

Table 4: Mean (SD) C max and AUC 0-t of Carglumic Acid Following Single Oral Dose Administration of CARBAGLU 80 mg/kg or 40 mg/kg in Subjects with Renal Impairment and Matched Healthy Control Subjects with Normal Renal Function PK Parameters Normal Renal Function 1a : eGFR ≥90 mL/min/1.73m 2 (N=8) Mild Renal Impairment: eGFR 60-89 mL/min/1.73m 2 (N=8) Moderate Renal Impairment: eGFR 30-59 mL/min/1.73m 2 (N=8) Normal Renal Function 1b : eGFR ≥90 mL/min/1.73m 2 (N=8) Severe Renal Impairment: eGFR 15-29 mL/min/1.73m 2 (N=8) 80 mg/kg 40 mg/kg Treatment groups 1a and 1b represent two separate matched control groups of healthy subjects with normal renal function.

C max (ng/mL) 2983 (552) 4310 (1937) 6129 (1854) 1890 (901) 8377 (3815) AUC 0-t (ng*hr/mL) 28313 (6204) 39545 (12109) 79766 (19708) 20212 (6186) 143075 (55910) D ru g I n t erac ti o n S t ud i e s Based on in vitro studies, carglumic acid is not an inducer of CYP1A1/2, CYP2B6, CYP2C, and CYP3A4/5 enzymes, and not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 enzymes. Based on in vitro studies, carglumic acid is a substrate of the human OAT1 transporter. Carglumic acid is not a substrate of MDR1, BCRP, MATE1, MATE2-K, OAT1, OAT3, OATP1B1, OATP1B3, OCT1, and OCT2.

Carglumic acid is not an inhibitor of human BSEP, BCRP, MDR1, MATE1, MATE2-K, OAT1, OAT3, OATP1B1, OATP1B3, OCT1, and OCT2 transporters.

🧬 Pharmacodynamics 78 words ▾

12.2Pharmacodynamics In a retrospective review of the clinical course in 23 patients with NAGS deficiency, carglumic acid reduced plasma ammonia levels within 24 hours when administered with and without concomitant ammonia lowering therapies. No dose-response relationship has been identified. Cardiac Electrophysiology The effect of carglumic acid was evaluated in a Phase 1, randomized study in 76 healthy volunteers.

The study suggests a lack of clinically relevant QT prolongation effect at the highest therapeutic dose level (250 mg/kg/day).

🔬 Clinical Studies ~3 min read ▾

14. CLINICAL STUDIES

14.1Acute and Chronic Hyperammonemia due to NAGS Deficiency The efficacy of CARBAGLU in the treatment of acute and chronic hyperammonemia due to NAGS deficiency was evaluated in a retrospective case series of 23 NAGS deficiency patients treated with CARBAGLU over a median duration of 7.9 years (range 0.6 to 20.8 years). For acute treatment, patients received CARBAGLU at 100 mg/kg/day to 250 mg/kg/day orally administered in 2 to 4 divided doses. For maintenance treatment, the dosage was reduced over time based on plasma ammonia level and clinical response.

The baseline characteristics of the patient population are shown in Table 5 . Table 5: Baseline Characteristics of 23 NAGS Deficiency Patients Treated with CARBAGLU Patients N=23 Sex Male 14 (61%) Female 9 (39%) Age at initiation of CARBAGLU therapy (years) Mean (SD) 2 (4) Min-Max 0-13 Age groups at initiation of CARBAGLU therapy <30 days 9 (39%) >30 days - 11 months 9 (39%) ≥1 - 13 years 5 (22%) NAGS gene mutations by DNA testing Homozygous 14 (61%) Heterozygous 4 (17%) Not available 5 (22%) Patients current treatment status On-going 18 (78%) Discontinued 5 (22%) The clinical and biochemical data in the 23-patient case series were retrospectively collected, unblinded and uncontrolled and preclude formal statistical testing.

Short-term efficacy was evaluated using mean and median change in plasma ammonia levels from baseline to days 1 to 3. Persistence of the effect was evaluated using long-term mean and median change in plasma ammonia level. Of the 23 NAGS deficiency patients in the case series, 13 patients had documented plasma ammonia levels prior to CARBAGLU treatment and after long-term treatment with CARBAGLU and were evaluable.

Table 5 summarizes the plasma ammonia levels at baseline, days 1 to 3 post-CARBAGLU treatment, and long-term CARBAGLU treatment (mean 8 years) in the 13 evaluable patients. All 13 patients had increased plasma ammonia levels at baseline (mean 271 micromol/L; normal range: 5 to 50 micromol/L). By day 3 and with long-term treatment, normal plasma ammonia levels were attained ( Table 6 ).

Table 6: Plasma Ammonia Levels in NAGS Deficiency Patients at Baseline and After Treatment with CARBAGLU Timepoint Patients (N = 13) Ammonia level (micromol/L) Baseline (prior to first dose of CARBAGLU) N 13 Mean (SD) 271 (359) Median 157 Range 72-1428 Missing Data 0 Day 1 N 10 Mean (SD) 181 (358) Median 65 Range 25-1190 Missing Data 3 Day 2 N 8 Mean (SD) 69 (78) Median 44 Range 11-255 Missing Data 5 Day 3 N 5 Mean (SD) 27 (11) Median 25 Range 12-42 Missing Data 8 Long-term treatment (mean duration 8 years; median duration 6 years; range 1-16 years based on last available value while on CARBAGLU treatment) N 13 Mean (SD) 23 (7) Median 24 Range 9-34 Missing Data 0 The mean plasma ammonia level at baseline and the decline that is observed after treatment with CARBAGLU in 13 evaluable patients with NAGS deficiency is illustrated in Figure 1 .

Figure 1: Mean Plasma Ammonia in 13 Evaluable NAGS Deficiency Patients at Baseline and After Treatment with CARBAGLU ammonia response chart

14.2Acute Hyperammonemia due to PA and MMA A randomized, double-blind, placebo-controlled, multicenter clinical trial evaluated the efficacy of CARBAGLU in the treatment of hyperammonemia in patients with PA and MMA (NCT01599286). Eligible hyperammonemic episodes, defined as an admission to the hospital with a plasma ammonia level ≥ 70 micromol/L, were randomized 1:1 to receive either CARBAGLU or placebo for 7 days or until hospital discharge, whichever occurred earlier. All patients received standard of care, including a combination of protein restriction, intravenous glucose, insulin, and/or L-carnitine; the use of alternative pathway medications (e.g., sodium benzoate and medications with phenylacetate as an active metabolite) was prohibited.

CARBAGLU was dosed orally at 150 mg/kg/day for patients ≤ 15 kg or 3.3 g/m 2 /day for patients > 15 kg and was divided into 2… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 138 words ▾

13. NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of carglumic acid was assessed in a 2-year carcinogenicity study in rats. Carglumic acid was not tumorigenic at oral doses up to 1000 mg/kg/day (approximately 34 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC). Carglumic acid was negative in the Ames test, chromosomal aberration assay in human lymphocytes, and the in vivo micronucleus assay in rats.

There were no effects on fertility or reproductive performance in female rats at oral doses up to 2000 mg/kg/day (approximately 38 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC). In a separate study, mating and fertility were unaffected in male rats at oral doses up to 1000 mg/kg/day (approximately 34 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 135 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of carglumic acid was assessed in a 2-year carcinogenicity study in rats. Carglumic acid was not tumorigenic at oral doses up to 1000 mg/kg/day (approximately 34 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC). Carglumic acid was negative in the Ames test, chromosomal aberration assay in human lymphocytes, and the in vivo micronucleus assay in rats.

There were no effects on fertility or reproductive performance in female rats at oral doses up to 2000 mg/kg/day (approximately 38 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC). In a separate study, mating and fertility were unaffected in male rats at oral doses up to 1000 mg/kg/day (approximately 34 times the maximum reported human maintenance dose [100 mg/kg/day] based on AUC).

📄 Patient Package Insert ~3 min read ▾

INSTRUCTIONS FOR USE CARBAGLU ® (CAR-buh-gloo) (carglumic acid) Tablets for oral suspension Important information: CARBAGLU tablets for oral suspension (CARBAGLU tablet) must be mixed in water before taking . CARBAGLU tablets should not be mixed in any other food or liquid. Do not swallow CARBAGLU tablets whole.

Do not crush CARBAGLU tablets. Take CARBAGLU right before meals or feedings. The CARBAGLU tablet 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 CARBAGLU. The CARBAGLU 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 CARBAGLU tablets by mouth using a cup: Children and Adults 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. For example: If the prescribed dose is 2 CARBAGLU tablets, add a minimum of 5 mL of water into the cup. If the prescribed dose is 2 and a ¼ CARBAGLU tablets, add a minimum of 7.5 mL of water into the cup.

If the prescribed dose is 2 and a ½ CARBAGLU tablets, 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 CARBAGLU. Place the prescribed number of CARBAGLU tablets into the water in the cup.

Carefully stir the CARBAGLU tablet and water mixture in the cup to avoid spilling the mixture. CARBAGLU tablets do not dissolve completely in water. Swallow the CARBAGLU tablet and water mixture right away .

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 . Repeat step 5 until there are no pieces of the tablet left in the cup.

Taking CARBAGLU tablets by mouth using an oral syringe: Children 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. For example: If the prescribed dose is 2 CARBAGLU tablets, add a minimum of 5 mL of water into the cup. If the prescribed dose is 2 and a ¼ CARBAGLU tablets, add a minimum of 7.5 mL of water into the cup.

If the prescribed dose is 2 and a ½ CARBAGLU tablets, 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 CARBAGLU. Place the prescribed number of CARBAGLU tablets into the water in the cup.

Carefully stir the CARBAGLU tablet and water mixture in the cup to avoid spilling the mixture. CARBAGLU tablets do not dissolve completely in water. Draw up all of the CARBAGLU tablet and water mixture in the cup into an oral syringe.

Give your child the CARBAGLU tablet 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. 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 . Repeat step 6 until there are no pieces of the tablet left in the oral syringe. Giving CARBAGLU tablets through a nasogastric (NG) or gastrostomy tube (G-tube): Children and Adults 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.

For example: If the prescribed dose is 2 CARBAGLU tablets, add a minimum of 5 mL of water into the cup. If the prescribed dose is 2 and a ¼ CARBAGLU tablets, add a minimum of 7.5 mL of water into the cup. If the prescribed dose is 2 and a ½ CARBAGLU tablets, add a minimum of 7.5 mL of water into the cup.

Ask your healthcare provider if yo… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 219 words ▾

PACKAGING AND LABELING NDC 52276-312-60 Carbaglu ® 200 mg carglumic acid tablets for oral suspension 60 Tablets Rx only Before opening, store refrigerated at 2°C – 8°C (36°F – 46°F). Do not refrigerate. Do not store above 30°C (86°F).

Discard one month after first opening Date of first opening. 4022649 5/1344 NDC 52276-312-60 Carbaglu ® 200 mg carglumic acid tablets for oral suspension 60 Tablets Rx only Disperse CARBAGLU tablets in water. Do not swallow whole or crushed.

Supplied by: Recordati Rare Diseases Puteaux, France Distributed by: Recordati Rare Diseases Inc. Lebanon, NJ 08833 USA RECORDATI RARE DISEASES Group NDC 52276-312-05 Carbaglu ® 200 mg carglumic acid tablets for oral suspension 5 Tablets Rx only Before opening, store refrigerated at 2°C – 8°C (36°F – 46°F). Do not refrigerate.

Do not store above 30°C (86°F). Discard one month after first opening Date of first opening. 4022647 5/1142 NDC 52276-312-05 Carbaglu ® 200 mg carglumic acid tablets for oral suspension 5 Tablets Rx only Disperse CARBAGLU tablets in water.

Do not swallow whole or crushed. Supplied by: Recordati Rare Diseases Puteaux, France Distributed by: Recordati Rare Diseases Inc. Lebanon, NJ 08833 USA RECORDATI RARE DISEASES Group Carbaglu bottle label - 60 Tablets Carbaglu carton label - 60 Tablets Carbaglu bottle label - 5 Tablets Carbaglu carton label - 5 Tablets

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
60 tablets52276-0312-60 312 Rx · $19,383,505
5 tablets this page52276-0312-05 No Medicaid data
Drug total (last 4 qtrs): 312 Rx · 86,108 units · $19,383,505 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Carbaglu — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Carbaglu. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$2M
Claims incl. refills
14
Beneficiaries
—
Spend / beneficiary
—
Spend / claim
$142,717.12
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Recordati Rare Diseases. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 60 tablets (52276-0312-60). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Recordati Rare Diseases is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 52272-0001-01 · Albright 52276-0400-01 · Recordati →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.