This package insert follows the Pharmaceuticals, Medical devices and Other Therapeutic Products Act of Japan.
In Vitro Diagnostics
Marketing Approval No. 22500AMX01789000**Revised: December 2019 (3rd edition)* Revised: January 2017 (2nd edition)

This package insert must be read carefully prior to use.
Topiramate assay kit(Classification No.: 83023000)

aggregation as the absorbance.
Sample (topiramate) + Anti-topiramate antibody─────▶ Antigen-antibody reaction

Nanopia TDM Topiramate

Unreacted anti-topiramate antibody + Topiramatecoated latex───▶ Aggregation by antigen-antibody reaction

General Precautions
1. Whether measurement with this product isnecessary should be determined in consideration of
the patient’s symptoms and response to treatment.
2. This product is for in vitro diagnostic use, and mustnot be used for any other purposes.
3. Clinicians should make a comprehensive clinicaldecision based on assay results in conjunction withclinical symptoms and other examination results.
4.Please read carefully the "PRECAUTIONS" section,
particularly under "Effects on Laboratory Tests" ofthe package insert of each drug, for information on
the influence to the assay result that medications
administered to the patient have. Please also read
carefully the "2. Interfering Substances," in the"Procedural Precautions" section, as well as "2.
Precautions for Assessment" in the "Assessment of
Assay Results" section, of this package insert.
5. This product should be used only as directed in thispackage insert. Reliability of results cannot be
guaranteed if there are any deviations from the
instructions in this package insert.
6. 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.
7. 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.
8. Perform a quality control test prior to assay toensure accuracy.

2. Features
1) Liquid reagents, ready-to-use.
2) Applicable to various automated analyzers.
Procedural Precautions ＊1. Properties of Samples and Sampling Methods
1) Samples
Serum and plasma (EDTA plasma) may be used.
2) Storage of samples(1) After separation of serum (plasma), samples
may be stored for up to 7 days in a refrigerator.
If samples cannot be measured within 7 daysof serum (plasma) separation, store them at−20C and measure them within 21 days.
Stored samples should be brought to room
temperature (15–30C) before use.
(2) Samples may be frozen and thawed up to
twice.
3) Sampling should be performed after removing
insoluble matter from the sample. Very cloudy
specimens should be centrifuged before assay.
2. Interfering substances
1) Assay results are not affected by free bilirubin(up to 20.8 mg/dL), conjugated bilirubin (up to
20.0 mg/dL), hemoglobin (up to 484 mg/dL),
formazin turbidity (up to 1430 FTU), or
rheumatoid factors (up to 500 IU/mL).
2) 9-Hydroxytopiramate is a metabolite of
topiramate that can affect assay values.
However, the metabolite has no influence on
assay values obtained with this product,
because it is usually detected in the urine andits serum or plasma concentration is low.1) ,2)
Concentra
Cross-tion
reactivity
Metabolite
tested※(%)(µg/mL)
4.00
19.75
98.00
22.63
Hydroxytopiramate
32.00
15.56

Description (Kit Components)
Component: Ingredients
TPM Antibody Solution 1:
Anti-topiramate sheep polyclonal
antibody
TPM Latex Regent 2:
Topiramate-coated latex
Intended Use
Measurement of topiramate in serum or plasma
Assay Principle
1. Assay Principle
When a certain amount of anti-topiramate antibody
is added and reacted with a sample, consumptionof the antibody depends on its content in thesample. When topiramate-coated latex is added,
residual anti-topiramate antibody reacts with thelatex and forms aggregates. Since the extent of
aggregation depends on the topiramate
concentration in the sample, the topiramate
concentration can be determined by measuring

3) If each concomitant drug is at the concentration
shown in the table below when the topiramate
concentration is approximately 5 μg/mL, crossreactivity is as follows.

12. Assay Procedure
This product is compatible with various types ofautomated analyzer. An example of the assay
procedure is indicated below.

Concentra
Cross-tion
reactivity※
tested(%)(µg/mL)
Acetaminophen
31
0.74
Acetazolamide
40
0.33
Alprazolam
2.00
0.50
Amitriptyline
1–2.00
Acetylsalicylic acid598
0.02
Atenolol
10.33
1.84
Caffeine60–0.05
Carbamazepine30
0.93
Clonazepam
0.18–11.11Clorazepate
2.00
4.50
Diazepam
5.1
0.00
Dichlorphenamide
32.00
0.38
Ethosuximide
252
0.15
Famotidine
0.97
9.28
Flurazepam
17.50
0.63
Furosemide
3.70
2.97
Gabapentin
93
0.22
Hydrochlorothiazide
6.00
2.17
Ibuprofen
500
0.09
Lamotrigine
45
0.22
Levetiracetam
124
0.11
Metoprolol
5.25
0.76
Nadolol121
0.23
Naproxen
509
0.02
Nortriptyline
1
2.00
Phenobarbital
40
0.23
Phenytoin
20
5.50
Primidone
40
0.58
Salicylic acid598
0.03
Tolbutamide
642
0.02
Valproic acid100.67–0.06
Verapamil
2
4.50
Zonisamide
122
0.09
※
Based on the Clinical and Laboratory Standards
Institute (CLSI) EP7-A2, cross-reactivity wascalculated by the following equation.
Cross-reactivity (%) = ({[Concentration of
topiramate in the sample after adding themetabolite or drug] – [Concentration of
topiramate in the sample without the metabolite
or concomitant drug]} / [Concentration of themetabolite or drug in the sample]) × 100
3. Others
1) Always use Topiramate Calibrator for Nanopia
for calibration.
2) Precautions for assay range
If the concentration in the sample exceeds themeasurement range, dilute the sample with theTopiramate Calibrator A for Nanopia (0.0 µg/mL) and perform re-measurement.
Drug name

37C
37C
Reagent
Sample Reagent
Measurement(2)
3 μL + (1)Approx.
Approx. (Absorbance I※)
180 μL120 μL
5 min
1 min
37C
Measurement
Approx. (Absorbance II※)
2 min
Calculation ofconcentration※

Absorbance I and II: Absorbance at 700 nm

Calibration material: Topiramate Calibrator for
Nanopia (Manufacture's assigned value)
Assessment of Assay Results ＊＊1. Reference standard range
The standard of effective blood concentration of
topiramate is considered as 5–20 μg/mL, but it has
been reported that it is also effective lower than 5
μg/mL4). Assay results should be assessed while
taking into consideration the patient’s clinicalfindings and other laboratory data.
It is recommended that the blood concentration of
topiramate should be measured in a sufficientnumber of samples for statistical analysis and thatits clinical effective concentration should bedetermined by each medical institution.
2. Precautions for Assessment
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.
Clinical Significance ＊＊Topiramate is an antiepileptic drug with a sulfamate
structure in a fructopyranose skeleton. It is used in
combination with other antiepileptic drugs for thetreatment of partial seizures (including secondary
generalized seizures) in patients for whom the otherantiepileptic drugs are not sufficiently effective.
The main adverse reactions to topiramate are reported
to be somnolence, weight loss, dizziness, anorexia,
and bulimia syndrome. Serious adverse reactions
include secondary angle closure glaucoma, acutemyopia due to secondary angle closure glaucoma,
renal and urinary calculus, metabolic acidosis,
hypohidrosis, and hyperthermia secondary tohypohidrosis.
It was reported overseas that the incidence of adverse
events in the early period after starting topiramate
therapy could be reduced by decreasing the initial
dosage and by slower dose escalation (e.g., the initial
dosage was set at 50 mg/day and then was increased
by 50 mg each every week). Therefore, before starting
treatment with topiramate it is necessary to consider
whether the initial dose should be 50 mg/day
depending on the condition of the patient and whether
dose escalation should be modified from 100 mg/day

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

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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) After completion of measurement, this productshould be tightly stoppered and stored in arefrigerator.
5) Do not mix materials from different kit lot
numbers.
6) 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) Sodium azide has been added as an antiseptic
agent in this product. It can react with lead orcopper pipes to produce the highly explosive
metal azide. Therefore, the reagent should beflushed with large amounts of water during
disposal.
4. Other precautions
Do not use the containers for other purposes.

to 50 mg/day.3） It is recommended to measure theblood concentration of topiramate and adjust the
dosage carefully in patients with renal dysfunction(Creatinine clearance < 70 mL/min), in whom theblood concentration of topiramate is considered tofluctuate, and the patients used in conjunction withCYP3A4 revulsive or hydrochlorothiazide.4)
Monitoring the blood concentration is considered to be
especially important when adverse reactions occur,
seizures cannot be controlled, compliance needs to be
confirmed, pregnancy is expected, and during
pregnancy.5)

Assay results (Nanopia TDM Topiramate)

Performance
1. Sensitivity
1) Absorbance of standard solution (0.0 µg/mL) is≥ 1900 (Abs. × 10000).
2) The difference of absorbance between standard
solution (0.0 µg/mL) and another standard
solution (2.0 µg/mL) is ≥ 500 (Abs. × 10000).
2. Accuracy: 80–120 % of the expected assay value
3. Within-run Reproducibility:
Coefficient of variation ≤ 15 %(Test methods used for 1.–3. are in-house methods.)
4. Measurement Range6): (On Hitachi 7180
automated analyzer)
1.5–32.0 μg /mL
5. Correlation6)
Serum
N = 199, r = 0.989, y (obtained with Nanopia TDM
Topiramate) = 1.09x (obtained by the control
method) + 0.38
Control method: LC/MS/MS

Storage and Shelf Life ＊1. Storage temperature: 2–8C
2. Shelf life: 18 months from the date of manufacture(The expiration date is printed on the outer
package.)
PackagingName
TPM Antibody
Nanopia TDM Solution 1
Topiramate
TPM Latex
Reagent 2

Assay results (LC/MS/MS)

6. Standard Material
Topiramate (in-house standard material)
Precautions for Use or Handling ＊1. Precautions for Handling (to Ensure Safety)
1) All samples used in the test should be handled asa 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 TPM Antibody Solution 1 and TPM Latex
Reagent 2. Therefore, if the reagent comes inPackage1 × 18 mL
1 × 12 mL

References ＊＊1) Britzi M., Soback S., et al. ： Ther Drug Monit.
25(3),314-22(2003)
2) Britzi M., Perucca E., et al. ： Epilepsia. 46(3),378-84（2005）
3) Topina tablets 25mg, 50mg, 100mg package insert
4) Japanese Society of Therapeutic Drug Monitoring.
[Guideline for therapeutic drug monitoring (TDM)
for antiepileptic drug 2018]. Tokyo: Kanehara

3Shuppan; 2018. pp. 28-29, pp. 102-107.
5) Tsuji S. and Ukawa Y. (eds.): Epilepsy Textbook
New Version (1st edition), Tokyo, Nakayama
Shoten, 2012, pp. 204-205.
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

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