This package insert follows the Pharmaceuticals, Medical devices and Other Therapeutic Products Act of Japan.
In Vitro Diagnostics
Marketing Notification No. 13A2X00197218102**Revised: December 2019 (7th edition)*Revised: January 2017 (6th edition)

This package insert must be read carefully prior to use.
Carbamazepine assay kit(Classification No.: 30395000)

It has been reported that there is considerable
individual variation in the absorption, metabolism, andexcretion of carbamazepine, and the blood level of its
metabolite carbamazepine-10, 11-epoxide increases
significantly when carbamazepine is administeredwith other antiepileptic drugs.
Monitoring the blood level of carbamazepine is usefulfor avoiding toxicity and for obtaining optimal
efficacy by dose adjustment.1),3)

Nanopia TDM Carbamazepine
General Precautions
1. This product is for in vitro diagnostic use, and mustnot be used for any other purposes.
2. Clinicians should make a comprehensive clinicaldecision based on assay results in conjunction withclinical symptoms and other examination results.
3. This product should be used only as directed in thispackage insert. Reliability of results cannot be
guaranteed if there are any deviations from theinstructions in this package insert.
4. If the reagent accidentally comes in contact witheyes and/or mouth, rinse immediately with ample
water as first aid, and consult the doctor if required.
5. Carefully read the operating instructions for eachtype of automated analyzers prior to using thisproduct. Parameters for each type of analyzers areavailable, and can be requested from SEKISUIMEDICAL CO., LTD. if required.
6. Perform a quality control test prior to assay toensure accuracy.

Assay Principle
1. Assay Principle
When a certain amount of anti-carbamazepine
antibody is added and reacted with a sample,
consumption of the antibody depends on its content
in the sample. When carbamazepine-coated latex isadded, residual anti-carbamazepine antibody
reacts with the latex and forms aggregates.
Since the extent of aggregation depends on thecarbamazepine concentration in the sample, thecarbamazepine concentration can be determined bymeasuring aggregation as the change ofabsorbance.
Sample (carbamazepine) + Anti-carbamazepine
antibody ───────▶ Antigen-antibody reaction

Description (Kit Components)
Component: Ingredients
CBZ Antibody Solution 1:
Anti-carbamazepine mousemonoclonal antibody
CBZ Latex Reagent 2:
Carbamazepine-coated latex

Unreacted anti-carbamazepine antibody +Carbamazepine-coated latex────▶ Aggregation by antigen-antibody reaction
2. Features
1) Because a highly specific monoclonal antibody
is used, this product shows excellent sensitivity
and accuracy.
2) Liquid reagents, ready-to-use.
3) Applicable to various automated analyzers.

Intended Use ＊＊Measurement of carbamazepine in serum orplasma＊＊

Procedural Precautions ＊1. Properties of Samples and Sampling Methods
1) Samples
Serum and plasma (heparin plasma, EDTAplasma and citrated plasma) may be used.
2) Storage of samples
If serum or plasma samples cannot be measured
on the day of separation, store them as follows.
Avoid repetition of freezing and thawing.
2–8C: for tests within 7 days
≤ -20C: for tests within 3 months
Bring samples to room temperature (15–30C)
before use.
3) Caution must be exercised, because aseparating agent, etc. in the blood collection
tube may affect assay values.4)4) Sampling should be performed after
removing insoluble matter from the sample.
Highly turbid specimens should becentrifuged before assay.
2. Interfering substances
1) Assay results are not affected by free bilirubin

Carbamazepine (5H-dibenz [b, f] azepine-5carboxamide) is an antiepileptic drug widely used forthe treatment of trigeminal neuralgia,1 all types ofpartial seizures (simple partial seizures, complicatedpartial seizures, and secondary generalized seizures),and generalized tonic-clonic seizures. Approximately
70% of carbamazepine in the bloodstream is bound toplasma protein. Carbamazepine is metabolized toactive carbamazepine-10,11-epoxide and then tocarbamazepine-10,11-dihydroxide. These metabolites
are excreted in the urine. The plasma level ofcarbamazepine-10,11-epoxide is 15–48% of that of theparent compound,2) and its biological half-life (5–8hours) is shorter than that of carbamazepine (8 –60hours). Both metabolites are excreted in the urine,
either unchanged or as glucuronic acid conjugates.
Toxicities of carbamazepine can be dose-dependent or
dose-independent.1) Nystagmus, blood dyscrasia, andgastrointestinal disorders such as nausea, vomiting,and anorexia are dose-independent. Symptoms related
to the central nervous system such as dizziness anddiplopia are dose-dependent.

1(up to 20 mg/dL), conjugated bilirubin (up to 20mg/dL), hemoglobin (up to 500 mg/dL),ascorbic acid (up to 50 mg/dL), formazinturbidity (up to 2500 FTU), or rheumatoid
factors (up to 450 IU/mL).
2) Because mouse antibody is used in the assay,
artifactual elevation of results may occur if thesample contains human anti-mouse antibody. In
this case, perform re-measurement by anothermethod.
3) Cross-reactivity
The following table summarizes drugs related
to carbamazepine and cross-reactivity between
carbamazepine and other drugs.

CompoundConcentration
tested(µg/mL)
100
1000
25

This product is compatible with various types ofautomated analyzer. An example of the assay
procedure is indicated below.
37C Reagent 37CSample Reagent
Measurement+2 μL
(2)
(1)
270
70 (Absorbance I※)
220 μL sec 60 μL sec37C
Measurement
247 (Absorbance II※)sec
Calculation ofconcentration※

Crossreactivity (%)

Absorbance I and II: Absorbance at 600 nm

Calibration material: TDM Calibrator for Nanopia(manufacture's assigned value)＊＊

Assessment of Assay Results ＊1. Reference standard range
The effective therapeutic concentration ofcarbamazepine has been reported to be 4−12μg/mL2), 3), but when other antiepileptic drugs suchas phenobarbital or phenytoin are used inconjunction, the target blood concentration is set as
4 — 8 μg/mL. It has been reported that sedation
occurs when the single dose exceeds 10 μg/mL, butadverse reactions may also occur within thetherapeutic range.5) Therefore, interpretation ofassay results should also be based on the patient's
clinical findings and other examination results.
2. There may be reactions or interfering reactions
with non-target substances. If assay results appear
to be unreliable, repeat the measurement (ifnecessary, after dilution) or try another analyticalmethods.

Amitriptyline
6
Amobarbital
0.05
Carbamazepine-10,1131.6
epoxideClorazepate
2000
0.15Chlordiazepoxide
2000
0.07
Diazepam250
0.2
Ethosuximide
10000Ethotoin
10000.06
Glutethimide
1000
0p-Hydroxyphenobarbital
2000
0.01
5-(p-Hydroxyphenyl)10000.07
henylhydantoin
Imipramine
200
1.5
Mephenytoin
3000
0.03
Methsucimide
5000
0.02
Nortriptyline
50
24.2
Phenothyazine
200
0.2
2-Phenyl-21000
0.02ethylmalonamide
Phenytoin
4000Primidone
1000
0.01
Probenecid
500
0Promethazine
1500
0.02
Secobarbital
2000
0.02
Valproic acid
7000
0.01
3. Others
1) Always use TDM Calibrator for Nanopia
for calibration.
2) Precautions for assay range
If the concentration of a target substance in thesample exceeds the measurement range, dilutethe sample with a separately sold diluent(manufactured by SEKISUI MEDICAL CO.,LTD.), and perform re-measurement.

Performance ＊＊1. Sensitivity
1) The change of absorbance of the standardsolution (0 μg/mL) per minute is 0.090–0.230.
2) The ratio between the change of absorbance perminute with the standard solution (0 µg/mL)
and that with another standard solution (2µg/mL) is 50–85%.
2. Accuracy: 80–120 % of the expected assay value
3. Within-run Reproducibility:
Coefficient of variation ≤ 10 %(Test methods used for 1.–3. are in-house methods.)
4. Measurement Range6): (On Hitachi 7170S
automated analyzer)
0.4–20 μg/mL
5. Correlation6)
1) Serum
N=66
r=0.992
y=0.93x+0.25
Control method: Approved in vitro diagnostic(enzyme immunoassay)
2) Plasma
N=76
r=0.991y=0.97x–0.29
Control method: Approved in vitro diagnostic(enzyme immunoassay)
6. Standard Material
Carbamazepine (U.S. Pharmacopoeia)

Dosage/Administration (Assay Procedure) ＊1. Preparation of reagents
Reagent (1): CBZ Antibody Solution 1 is readyto use.
Reagent (2): CBZ Latex Reagent 2 is ready touse.
Before using this product, gently invert the CBZ
Latex Solution 2 bottle to mix it thoroughly, andcheck that there are no bubbles.
2. Assay Procedure

Precautions for Use or Handling ＊1. Precautions for Handling (to Ensure Safety)
1) All samples used in the test should be handled as2

a material possibly infected with HIV, HBV,HCV, or other viruses. To prevent infection, use
disposable gloves and avoid mouth pipetting
during the test.
2) Sodium azide is added as an antiseptic agent in
the CBZ Antibody Solution 1 and CBZ Latex
Reagent 2. Therefore, if the reagent comes in
accidentally contact with eyes, mouth or skin,rinse immediately with ample water as first aid,
and consult the doctor if required.
2. Precautions for use
1) This product should be stored as directed,without freezing. Freezing can deteriorate thereagents, which can produce inaccurate results.
Therefore, avoid using the reagents which havebeen previously frozen.
2) Do not use expired reagents. Use of suchreagents cannot guarantee the reliability ofmeasurement values.
3) Do not replenish the reagents.
4) Do not mix materials from different kit lotnumbers.
5) Do not perform the assay under direct sunlight
3. Precautions for Disposal
1) Before disposal, used samples and theircontainers must be immersed in sodium
hypochlorite solution at a concentration ofgreater than 0.1% for longer than 1 hour or
autoclaved at 121ºC for 20 minutes.
2) To prevent infections from spilled samples orsolutions containing samples, wipe the spilledarea thoroughly with disinfectants such as
sodium hypochlorite solution at a concentrationof greater than 0.1%.
3) The reagents and treated samples should bediscarded as medical waste or industrial waste
according to the waste disposal regulations.
4) The reagents should be disposed of inaccordance with the Water Pollution Control act
or related regulations.
5) Sodium azide has been added as an antiseptic
agent in the CBZ Antibody Solution 1 and CBZ
Latex Reagent 2. It can react with lead or copper
pipes to produce the highly explosive metal azide.
Therefore, the reagent should be flushed withlarge amounts of water during disposal.
4. Other precautions
Do not use the containers for other purposes.

＊＊References ＊1) Morselli P. C.: Carbamazepine: absorption
distribution and excretion, in complex partial
seizures and their treatment, Advances inNeurology. Vol.Ⅱ, edited by Penry J.K., Daly D.
D. New York, Raven Press, pp 279−393, 1975.
2) Warner A, Privitera M and Bates D.：Standards oflaboratory practice：antiepileptic drug monitoring.
Clin Chem. 44（ 5）, 1085−1095（1998）
3) Mackichan J. J., Kutt H.: Carbamazepine:
Therapeutic use and serum concentration
monitoring.: In Taylor, W.J., Finn, A.L. （eds.）:
Individualizing
Drug
Therapy:
PracticalApplications of Drug Monitoring, Gross,Townsend, Frank Inc., New York, 2: 1−25, 1981.
4) Sawada T. et al.: J Med Pharm Sci, 51(1), 131−141,2004.
5) The Japanese Society of Therapeutic Drug
Monitoring. [Guideline for therapeutic drug
monitoring (TDM) for antiepileptic drug 2018].
Tokyo: Kanehara Shuppan; 2018. pp. 12-13, pp.
49-56.
6) In house data, SEKISUI MEDICAL CO., LTD.
Contact
SEKISUI MEDICAL CO., LTD.
international@sekisui.com

Manufacturer ＊SEKISUI MEDICAL CO., LTD.
1-3, Nihonbashi 2-chome, Chuo-ku, Tokyo, Japan

Storage and Shelf Life ＊1. Storage temperature: 2–8C
2. Shelf life: 14 months from the date of manufacture(The expiration date is printed on the outer package.)
Packaging
NamePackage
CBZ Antibody
1 × 44 mL
Nanopia TDM Solution 1
Carbamazepine CBZ Latex
1 × 12 mL
Reagent 2
Constituent reagents are available in otherconfigurations. For further details please contact
SEKISUI MEDICAL CO., LTD.

3