1. INDICATIONS
AND USAGE
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, is recommended.
Chronic
Hyperammonemia in Patients with NAGS Deficiency
Carbaglu is
indicated as maintenance therapy in pediatric and adult patients for the
treatment of chronic hyperammonemia due to 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 needed
based on plasma ammonia levels.
2. DOSAGE AND
ADMINISTRATION
Carbaglu
treatment should be initiated by a physician experienced in metabolic
disorders. Based on clinical experience, the treatment may be started as early
as the first day of life.
Carbaglu tablets
are uncoated and should not be swallowed whole or crushed. Disperse Carbaglu
tablets in water immediately before use. For all preparations, use in other
foods and liquids has not been studied clinically and is therefore not
recommended.
Recommended
Dosage
Carbaglu should
be initiated as soon as the diagnosis of NAGS deficiency is suspected, which
may be as soon as at birth, and managed by a physician and medical team
experienced in metabolic disorders.
Initial
Dosage: The recommended initial daily dosage of Carbaglu in pediatric
and adult patients for acute hyperammonemia is 100 mg/kg to 250 mg/kg divided
into 2 to 4 doses and rounded to the nearest 100 mg (i.e., half of a Carbaglu
tablet). Concomitant administration of other ammonia lowering therapies is
recommended.
Maintenance
Dosage: The recommended daily maintenance dosage of Carbaglu in
pediatric and adult patients is 10 mg/kg to 100 mg/kg divided into 2 to 4 doses
and rounded to the nearest 100 mg (i.e., half of a Carbaglu tablet).
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.).
Preparation and
Administration
Disperse Carbaglu tablets in water. Do not
swallow whole or crushed.Mix each 200 mg tablet in a minimum of 2.5 mL of
water to yield a concentration of 80 mg/mL.Carbaglu tablets do not dissolve completely in
water and undissolved particles of the tablet may remain in the mixing
container.Take Carbaglu immediately before meals or feedings.The Carbaglu suspension has a slightly acidic
taste.For all preparations, use in foods or liquids,
other than water, has not been studied clinically and is not recommended.
Preparation
for Oral Administration in Pediatric and Adult Patients
Add about 2.5 mL of water into a small cup for each
Carbaglu tablet or each ½ Carbaglu tablet needed for the prescribed dose.Add the Carbaglu tablets to the water in the cup.Carefully stir the tablet and water mixture.Swallow the mixture immediately. Pieces of the
tablet may remain in the cup.Rinse the cup with additional water and swallow the
mixture immediately. Repeat as needed until no pieces of the tablet are
left in the cup.
Preparation
for Nasogastric Tube Administration in Pediatric and Adult Patients
For patients
who have a nasogastric tube in place, Carbaglu should be administered as
follows:
Add about 2.5 mL of water into a small cup for each
Carbaglu tablet or each ½ Carbaglu tablet needed for the prescribed dose.Add the Carbaglu tablets to the water in the cup.Carefully stir the tablet and water mixture.Draw up the mixture into a catheter-tip syringe.Administer the mixture immediately through the
nasogastric (NG) tube. Pieces of the tablet may remain in the catheter-tip
syringe or NG tube.Flush immediately with 1 to 2 mL of additional
water to clear the NG tube.Flush the NG tube again, as needed, until no pieces
of the tablet are left in the syringe or NG tube.
Preparation
for Oral Administration Using an Oral Syringe in Pediatric Patients
For
administration via oral syringe, Carbaglu should be administered as follows:
Add about 2.5 mL of water into a small cup for each
Carbaglu tablet or each ½ Carbaglu tablet needed for the prescribed dose.Add the Carbaglu tablets to the water in the cup.Carefully stir the tablet and water mixture.Draw up the mixture in an oral syringe and administer
immediately. Pieces of the tablet may remain in the oral syringe.Refill the oral syringe with a minimum volume of
water (1 to 2 mL) and administer immediately.Flush the oral syringe again, as needed, until no
pieces of the tablet are left in the syringe.
3. DOSAGE FORMS
AND STRENGTHS
Carbaglu is a
white and elongated 200 mg tablet for oral suspension, functionally scored and
coded “C” on one side.
4.
CONTRAINDICATIONS
None
5. WARNINGS AND
PRECAUTIONS
Hyperammonemia
Any episode of
acute symptomatic hyperammonemia should be treated as a life-threatening
emergency. Treatment of severe hyperammonemia may require dialysis, preferably
hemodialysis and/or hemofiltration, to reduce plasma ammonia concentration.
Untreated hyperammonemia can result in brain damage and death, and prompt use
of all therapies necessary to reduce plasma ammonia level is essential.
Since
hyperammonemia in NAGS deficiency is the result of imbalance between ammonia
detoxification capacity and protein catabolism, complete protein restriction
during an acute hyperammonemic episode is recommended for no longer than 12 to
36 hours while maximizing caloric supplementation to reverse catabolism.
Protein should be reintroduced as early as possible, following improvement of
metabolic and clinical abnormalities in this setting. During long-term
management, dietary protein restriction should be instituted to maintain blood
ammonia level within an acceptable range for age.
Ongoing
monitoring of plasma ammonia level, neurological status, growth parameters,
protein intake/nutritional status (both during acute hyperammonemic episodes
and long-term), and relevant laboratory tests in patients receiving Carbaglu
should be part of evaluating the clinical response to treatment.
6. ADVERSE
REACTIONS
Clinical 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.
Table 1 summarizes adverse reactions
occurring in 2 or more patients treated with Carbaglu in the retrospective case
series (≥ 9%).
Table 1: Adverse Reactions Reported in ≥ 2 Patients in
the Retrospective Case Series Treated with Carbaglu
|
|
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
|
2 (9)
|
|
Dysguesia
|
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)
|
8. USE IN
SPECIFIC POPULATIONS
Pregnancy
Pregnancy
Category C
There are no
adequate and well controlled studies or available human data with Carbaglu in
pregnant women. Decreased survival and growth occurred in offspring born to
animals that received carglumic acid at a dose approximately 38 times the
maximum reported human maintenance dose. Because untreated N-acetylglutamate
synthase (NAGS) deficiency results in irreversible neurologic damage and death,
women with NAGS must remain on treatment throughout pregnancy.
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).
In a peri- and
post-natal developmental study, female rats received oral carglumic acid from
organogenesis through lactation at doses of 500 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).
Nursing Mothers
It is not known
whether Carbaglu is excreted in human milk. Carglumic acid is excreted in rat
milk, and an increase in mortality and impairment of body weight gain occurred
in neonatal rats nursed by mothers receiving carglumic acid. Because many drugs
are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from Carbaglu, breast-feeding is not recommended.
Treatment is continuous and life-long for NAGS deficiency patients.
Pediatric Use
The efficacy of
Carbaglu for the treatment of hyperammonemia in patients with NAGS deficiency
from birth to adulthood was evaluated in a retrospective review of the clinical
course of 23 NAGS deficiency patients who all began Carbaglu treatment during
infancy or childhood. There are no apparent differences in clinical response
between adults and pediatric NAGS deficiency patients treated with Carbaglu,
however, data are limited.
Geriatric Use
Carbaglu has not
been studied in the geriatric population. Therefore, the safety and
effectiveness in geriatric patients have not been established.
10. OVERDOSAGE
One patient
treated with 650 mg/kg/day of carglumic acid developed symptoms characterized
as a monosodium glutamate intoxication-like syndrome: tachycardia, profuse
sweating, increased bronchial secretion, increased body temperature and
restlessness. These symptoms resolved upon reduction of dose.
Repeated oral
dosing of carglumic acid at 2000 mg/kg/day was lethal to most neonatal rats
within 2-3 days of treatment. The plasma concentrations that produced lethality
were not measured. In adult rats, a single oral administration of carglumic
acid was not lethal at doses up to 2800 mg/kg (approximately 20 times the
maximum starting dose based on C max).
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, practically
insoluble in organic solvents.
Chemically
carglumic acid is N-carbamoyl-L-glutamic acid or (2S)-2-(carbamoylamino)
pentanedioic acid, with a molecular weight of 190.16.
The structural
formula is:
Molecular
Formula: C 6H 10N 2O 5
The inactive
ingredients of Carbaglu are croscarmellose sodium, hypromellose,
microcrystalline cellulose, silica colloidal anhydrous, sodium lauryl sulfate,
sodium stearyl fumarate.
12. CLINICAL
PHARMACOLOGY
Mechanism 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 an 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 in patients with NAGS deficiency, thereby removing the
block in the urea cycle and facilitating ammonia detoxification and urea
production.
Pharmacodynamics
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.
Pharmacokinetics
The
pharmacokinetics of carglumic acid have been studied in healthy male subjects
using both radiolabeled and non-radiolabeled carglumic acid.
Absorption
The median Tmax
of Carbaglu was 3 hours (range: 2 to 4 hours). Absolute bioavailability has not
been determined.
Distribution
The apparent
volume of distribution was 2657 L (range: 1616-5797). Protein binding has not
been determined.
Elimination
Metabolism
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
Median value for
the terminal half-life was 5.6 hours (range 4.3 to 9.5 hours), the apparent
total clearance was 5.7 L/min (range 3.0 to 9.7 L/min), the renal clearance was
290 mL/min (range 204 to 445 mL/min), and the 24-hour urinary excretion was
4.5% of the dose (range 3.5 to 7.5%). Following administration of a single
radiolabeled oral dose of 100 mg/kg of body weight, 9% of the dose was excreted
unchanged in the urine and up to 60% of the dose was excreted unchanged in the
feces.
Drug Interaction
Studies
No drug
interaction studies have been performed. Based on in vitro studies,
Carbaglu 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.
13. NONCLINICAL
TOXICOLOGY
Carcinogenesis,
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).
14. CLINICAL
STUDIES
Responses of
Patients with NAGS Deficiency to Acute and Chronic Treatment
The efficacy of
Carbaglu in the treatment of hyperammonemia due to NAGS deficiency was
evaluated in a retrospective review of the clinical course of 23 NAGS
deficiency patients who received Carbaglu treatment for a median of 7.9 years
(range 0.6 to 20.8 years). Treatment with Carbaglu was divided in two regimens.
For acute treatment, patients received a total daily dose of 100 to 250 mg/kg
per day primarily administered in 2 to 4 divided doses for the first few days
of treatment. For maintenance treatment, the dosage was reduced over time based
upon biochemical and clinical responses.
The demographics
characteristics of the patient population are shown in Table 2.
Table 2: Baseline Characteristics of the 23 NAGS
deficiency patients
|
|
|
Patients
N=23
|
|
Gender
|
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
observations in the 23 patient case series were retrospective, unblinded and
uncontrolled and preclude any meaningful formal statistical analyses of the
data. However, short-term efficacy was evaluated using mean and median change
in plasma ammonia levels from baseline to days 1 to 3. Persistence of efficacy
was evaluated using long-term mean and median change in plasma ammonia
level. Table 3 summarizes the plasma ammonia
levels at baseline, days 1 to 3 post-Carbaglu treatment, and long-term Carbaglu
treatment for 13 evaluable patients. Of the 23 NAGS deficiency patients who
received treatment with Carbaglu, a subset of 13 patients who had both well
documented plasma ammonia levels prior to Carbaglu treatment and after
long-term treatment with Carbaglu were selected for analysis.
All 13 patients
had abnormal ammonia levels at baseline. The overall mean baseline plasma
ammonia level was 271 micromol/L. By day 3, normal plasma ammonia levels were
attained in patients for whom data were available. Long-term efficacy was
measured using the last reported plasma ammonia level for each of the 13
patients analyzed (median length of treatment was 6 years; range 1 to 16
years). The mean and median ammonia levels were 23 micromol/L and 24
micromol/L, respectively, after a mean treatment duration of 8 years.
Table 3: Plasma ammonia levels at baseline and after
treatment with Carbaglu
|
|
*13/23 patients with complete short-term and long-term
plasma ammonia documentation
**Mean ammonia normal range: 5 to 50 micromol/L
|
|
Timepoint
|
Statistics (N = 13*)
|
Ammonia** (micromol/L)
|
|
|
|
|
Baseline
(prior to first treatment with 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
Mean: 8 years
Median: 6 years
1 to 16 years
(last available value 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:
Ammonia response for 13 evaluable NAGS deficiency patients at baseline and after treatment
with Carbaglu
16. HOW
SUPPLIED/STORAGE AND HANDLING
How Supplied
Carbaglu is a
white and elongated 200 mg tablet for oral suspension, functionally scored and
coded “C” on one side.
Carbaglu is
available in 5 or 60 tablets in a high density polyethylene bottle with child
resistant polypropylene cap and desiccant unit.
NDC 52276-312-05
Bottles of 5 tablets
NDC 52276-312-60
Bottles of 60 tablets
Storage
Store in the
original unopened container at 2 – 8 °C (36 – 46 °F).
After first
opening of the container:
Do
not refrigerate, store at room temperature between 15 – 30°C (59 – 86°F).Keep
the container tightly closed between openings in order to protect from
moisture.Write
the date of opening on the tablet container.Do
not use after the expiration date stated on the tablet container.Discard
one month after first opening.
17. PATIENT
COUNSELING INFORMATION
Advise the
patient to read the FDA-approved patient labeling (Instructions for Use).
Preparation and
Administration
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, as described in the Instructions for Use.
Storage
Store
UNOPENED container in a refrigerator at 2 to 8 °C (36 to 46 °F).fter
first opening of the container: do not refrigerate, store at room
temperature between 15 to 30°C (59 to 86°F). Keep the container tightly
closed in order to protect from moisture. Write the date of opening on the
tablet container. Discard one month after first opening. Do not use after
the expiration date stated on the tablet container.
Lactation
Advise
women not to breast-feed during treatment with Carbaglu [see
Use in Specific Populations ( 8.3)] .
Supplied by:
Orphan Europe
SARL
Puteaux, France
Licensed to and
Distributed by:
Recordati Rare
Diseases Inc.
Lebanon, NJ 08833
For drug or
ordering information please call Accredo Health Group Inc., Customer Service at
1-888-454-8860.
Carbaglu ® is a
licensed trademark of Recordati Rare Diseases Inc.
This product
label may have been updated. For the most recent prescribing information,
please visit www.recordatirarediseases.com or www.Carbaglu.net.
INSTRUCTIONS FOR
USE
Carbaglu
(CAR-buh-gloo)
(carglumic acid)
tablet for oral
suspension
Important
information:
Carbaglu tablet 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 your dose of Carbaglu.
Taking Carbaglu
tablets by mouth using a cup:
Children and
Adults
1. Add about 2.5 mL
of water into a small cup for each Carbaglu tablet, or each ½ Carbaglu tablet,
needed for the prescribed dose. For example, if the prescribed dose is 2
Carbaglu tablets, add about 5 mL of water into the cup. If the prescribed dose
is 2½ Carbaglu tablets, add about 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.
2. Place the
prescribed number of Carbaglu tablets into the water in the cup.
3. Carefully stir
the Carbaglu tablet and water mixture in the cup to avoid spilling the mixture.
Carbaglu tablets do not dissolve completely in water.
4. Swallow the
Carbaglu tablet 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 Carbaglu
tablets by mouth using an oral syringe:
Children
1. Add about 2.5 mL
of water into a small cup for each Carbaglu tablet, or each ½ Carbaglu tablet,
needed for the prescribed dose. For example, if the prescribed dose is 2
Carbaglu tablets, add about 5 mL of water into the cup. If the prescribed dose
is 2½ Carbaglu tablets, add about 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.
2. Place the
prescribed number of Carbaglu tablets into the water in the cup.
3. Carefully stir
the Carbaglu tablet and water mixture in the cup to avoid spilling the mixture.
Carbaglu tablets do not dissolve completely in water.
4. Draw up all of
the Carbaglu tablet and water mixture in the cup into an oral syringe.
5. 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.
6. Pieces of the
tablet may remain in the oral syringe. Refill the oral syringe with at least 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 Carbaglu
tablets through a nasogastric (NG) tube:
Children and
Adults
1. Add about 2.5 mL
of water into a small cup for each Carbaglu tablet, or each ½ Carbaglu tablet,
needed for the prescribed dose. For example, if the prescribed dose is 2
Carbaglu tablets, add about 5 mL of water into the cup. If the prescribed dose
is 2½ Carbaglu tablets, add about 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.
2. Place the
prescribed number of Carbaglu tablets into the water in the cup.
3. Carefully stir
the Carbaglu tablet and water mixture in the cup to avoid spilling the mixture.
Carbaglu tablets do not dissolve completely in water.
4. Draw up all of
the Carbaglu tablet and water mixture in the cup into a catheter-tip syringe.
5. Connect the
catheter-tip syringe to the NG tube.
6. Give the Carbaglu
tablet and water mixture through the NG tube right away.
7. Pieces of the
tablet may remain in the catheter-tip syringe or NG tube. Refill the
catheter-tip syringe with 1 mL to 2 mL of water and flush the NG tube right away.
8. Repeat step 7
until there are no pieces of the tablet left in the catheter-tip syringe or NG
tube.
How should I
store Carbaglu?
Before opening, store Carbaglu in a refrigerator between
36°F to 46°F (2°C to 8°C) in the container it comes in.After opening, store Carbaglu at room temperature between
59°F to 86°F (15°C to 30°C). Do notstore Carbaglu in a
refrigerator.Keep
Carbaglu tablets in a tightly closed container to protect the tablets
from moisture.Write
the date the Carbaglu tablet container is opened on the container label.
Throw away any unused tablets one month after opening the tablet
container.Do
not use Carbaglu tablets after the expiration date on the tablet
container.
Keep Carbaglu
and all medicines out of the reach of children.
This
Instructions for Use has been approved by the U.S. Food and Drug
Administration.
Distributed by:
Recordati Rare
Diseases Inc.
Lebanon, NJ
08833
Carbaglu ® is a
licensed trademark of Recordati Rare Diseases Inc.
PACKAGING AND
LABELING
Carbaglu bottle
label - 60 Tablets in Bottle
Carbaglu carton
label - 60 Tablets in Bottle
Carbaglu bottle
label - 5 Tablets in Bottle
Carbaglu carton
label - 5 Tablets in Bottle
|
Carbaglu carglumic acid
tablet
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:52276-312
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
CARGLUMIC ACID (CARGLUMIC ACID)
|
CARGLUMIC ACID
|
200 mg
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
CELLULOSE,
MICROCRYSTALLINE
|
270 mg
|
|
SODIUM LAURYL SULFATE
|
0.5 mg
|
|
HYPROMELLOSES
|
4 mg
|
|
CROSCARMELLOSE SODIUM
|
19 mg
|
|
SILICON DIOXIDE
|
1.5 mg
|
|
SODIUM STEARYL FUMARATE
|
5 mg
|
|
|
Product Characteristics
|
|
Color
|
white (Bar-shaped)
|
Score
|
3 pieces
|
|
Shape
|
RECTANGLE (Bar-shaped)
|
Size
|
18mm
|
|
Flavor
|
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:52276-312-05
|
5 TABLET in 1 BOTTLE
|
|
|
2
|
NDC:52276-312-60
|
60 TABLET in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA022562
|
03/18/2010
|
|
|
|
Labeler - Orphan Europe, SARL (767598352)
|
|
Registrant - Orphan Europe, SARL (767598352)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Aesica Pharmaceuticals GmbH
|
|
341737465
|
manufacture(52276-312)
|
Revised: 11/2017
Orphan Europe,
SARL
