This package insert follows the Pharmaceuticals, Medical devices and Other Therapeutic Products Act of Japan.
In Vitro Diagnostics
Marketing Notification No. 13A2X00197220004**Revised: January 2017 (3rd edition)*Revised: February 2012 (2nd edition)

This package insert must be read carefully prior to use.
Digoxin assay kit(Classification No.: 30386000)

depends on the digoxin concentration in thesample, the digoxin concentration can bedetermined by measuring aggregation as thechange of absorbance.

Nanopia TDM Digoxin

Sample (digoxin) + Anti-digoxin antibody ────▶
Antigen-antibody reaction

General Precautions
1. This product is for in vitro diagnostic use, andmust not 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 ifrequired.
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.

Unreacted
anti-digoxin
antibody+Digoxin-coated latex ──── ▶ Aggregation byantigen-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.
＊＊

Procedural Precautions ＊1. Properties of Samples and Sampling Methods
1) Samples
Serum and plasma (heparin plasma, EDTA
plasma and citrated plasma) may be used. Do
not use whole blood.
2) Storage of samples2)
If serum or plasma samples cannot bemeasured on the day of separation, store themas follows. Avoid repetition of freezing andthawing.
2–8C: for tests within 1 week≤ -20C: for tests within 6 monthsBring 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.9)4) Sampling should be performed after removing
insoluble matter from the sample.
5) It has been reported that blood samples should
be collected at 12 hours after administration toaccurately evaluate the blood level ofdigoxin.3)
2. Interfering substances
1) Assay results are not affected by free bilirubin(up to 20 mg/dL), conjugated bilirubin (up to20 mg/dL), hemoglobin (up to 500 mg/dL),ascorbic acid (up to 50 mg/dL), or rheumatoid
factors (up to 500 U/L). If samples containchyle, artifactual elevation of the digoxin levelmay occur.
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 byanother method.
3) The following drugs and compounds show nocross-reactivity with this assay system at thefollowing concentrations.

Description (Kit Components)
Component: Ingredients
DIG Antibody Solution 1:Anti-digoxin mouse monoclonal
antibody
DIG Latex Reagent 2:
Digoxin-coated latex
Intended Use
Measurement of digoxin in serum or plasma
Digoxin is a digitalis product that enhances
myocardial contractility.1) It is most commonly used
for treatment of congestive cardiac failure andarrhythmias such as atrial fibrillation. The therapeutic
range of digoxin is narrow and individual variation
occurs with respect to the absorption, distribution,metabolism, and excretion of this drug. In addition,
the blood level relative to dosage is altered byconcomitant medications or changes of theunderlying disease. Monitoring the blood level ofdigoxin is effective for designing a regimens thatachieves appropriate efficacy while avoiding
symptoms of toxicity.2), 3)
Assay Principle
1. Assay Principle
When a certain amount of anti-digoxin antibody isadded and reacted with a sample, consumption of
the antibody depends on its content in the sample.
When digoxin-coated latex is added, residual
anti-digoxin antibody reacts with the latex andforms aggregates. Since the extent of aggregation

1Concentration(µg/mL)
Acetaminophen
1000
Cortisone
10Estriol
10
Phenytoin
100
Prednisone
10Progesterone
10
Secobarbital
100
Testosterone
517-α-OH-progesterone
10
Quinidine
100
Hydrochlorothiazide
100
Cortisol
10Dehydroisoandrosterone
10
Lidocaine
100
Prednisolone
10
Propranolol
100
Spironolactone
10
Phenobarbital
100
Procainamide
10011-OH-progesterone
10Ouabain octahydrate
0.15
Furosemide504) Cross-reactivity with the following cardiac
glycosides and their metabolites is as follows.
ConcenCrossSubstancetrationreactivity(µg/mL)(%)
Digoxigenin
50
3.6
Digoxigenin-bis5
108.0
digitoxoside
Digoxigenin582.0
mono-digitoxoside
Digitoxin50
4.4
Digitoxigenin
5000.7
D-(+)-digitoxose
100000Gitoxin
1500.5
3. Others
1) Use the calibrator designated by SEKISUIMEDICAL as the calibration material.
2) Precautions for assay range
If the digoxin concentration in the sample
exceeds the measurement range, dilute thesample with the Negative Calibrator
designated by SEKISUI MEDICAL andperform re-measurement.
Do not use any other solution for dilution.
Substance

Sample +10 μL

37C Reagent 37CReagent(2)
Measurement(1)570 μL 36 (Absorbance I※)
210 μL min
sec
37C
Measurement
4 (Absorbance II※)
min24
sec
Calculation ofconcentration※

Absorbance I and II: Absorbance at 700 nm

Calibration material: Calibrator designated bySEKISUI MEDICAL (manufacture's assignedvalue)
Assessment of Assay Results ＊＊1. Therapeutic range
The therapeutic range of digoxin is reported to be(0.5)–1.5
ng/mL
takingsafetyinto
consideration.10 At concentrations ≥ 1.5 ng/mL,
extracardiac symptoms of digitalis intoxication
may occur.10
2. Interpretation of results
The blood level of digoxin is affected by thesampling time; dosage; dosage form; method ofadministration; concomitant medications; and theabsorption,distribution,metabolism,andelimination of individual drugs. Therefore, assay
results should be interpreted carefully by taking
the influence of these factors into consideration.
The correlation between the blood concentrationand the clinical response also vary with age, renal
function, thyroid function, type and severity ofheart disease, and concomitant medications.
The therapeutic range is only a general guide.
Assay results and data should be interpreted
carefully while taking the symptoms of eachpatient into consideration.
3. 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.
Performance
1. Sensitivity
1) The difference in absorbance between
standard solution (0.5 ng/mL) and anotherstandard solution (0 ng/mL) is ≥ 0.03.
2) The difference in absorbance between standard
solution (5 ng/mL) and another standard
solution (0.5 ng/mL) is ≥ 0.15.
2. Accuracy: 85–115 % of the expected assay value
3. Within-run Reproducibility:
Coefficient of variation ≤ 15 %(Test methods used for 1.–3. are in-housemethods.)
4. Measurement Range11): (On Hitachi 7170S
automated analyzer)
0.2–5 ng /mL
5. Correlation11)
1) Serum N=40
r=0.991y=0.98x–0.01

Dosage/Administration (Assay Procedure) ＊＊1. Preparation of reagents
Reagent (1): DIG Antibody Solution 1 is readyto use.
Reagent (2): DIG Latex Reagent 2 is ready touse.
Before using this product, gently invert the DIG
Latex Reagent 2 bottle to mix it thoroughly, andcheck that there are no bubbles.
2. Assay Procedure
This product is compatible with various types ofautomated analyzer. An example of the assay
procedure is indicated below.

2

Control method: Approved in vitro diagnostic(enzyme immunoassay)
2) Plasma N=40
r=0.997
y=1.02x+0.03
Control method: Approved in vitro diagnostic(enzyme immunoassay)
6. Standard Material
Digoxin (U.S. Pharmacopoeia)

Packaging
NamePackage
DIG Antibody
1 × 42 mL
Solution 1
Nanopia TDMDigoxin
DIG Latex
1 × 14 mL
Reagent 2
Constituent reagents are available in otherconfigurations. For further details please contact
SEKISUI MEDICAL CO., LTD.

Precautions for Use or Handling ＊＊1. Precautions for Handling (to Ensure Safety)
1) All samples used in the test should be handled
as 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) Each of the constituent reagents contains
sodium azide as an antiseptic agent. Therefore,
if the reagent comes in accidentally contact witheyes, mouth or skin, rinse immediately withample 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 lot
numbers.
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) Each of the constituent reagents contains sodium
azide as an antiseptic agent. It can react withlead or copper pipes to produce the highly
explosive metal azide. Therefore, the reagent
should be flushed with large amounts of water
during disposal.
4. Other precautions
Do not use the containers for other purposes.

＊＊References ＊1) Lee KS et al.：Pharmacol. Rev. 23, 193（1971）
2) Lewis RP：Am. J. Cardiol. 69, 97G（1992）
3) Matzuk M. M. et al：Making Digoxin Therapeutic
Drug Monitoring More Effective, Ther. Drug
Monit., 13：215−219, 1991.
4) Keys PW et al.：Practical Applications of Drug
Monitoring, New York, Gross, Townsend andFrank,Inc. vol3, 1−21（1981）
5) Jogestrand T et al.：Am. Heart J. 117, 1076（1989）
6) Smith TW et al.：J. Clin. Invest. 49, 2377（1970）
7) Rainey PM：Am. J. Clin. Pathol. 92, 779（1990）
8) Valdes R：Clin. 31, 1525（1985）
9) Sawada T. et. al.: J Med Pharm Sci, 51(1),131−141, 2004.
10) Japanese Circulation Society/Japanese Society of
Therapeutic Drug Monitoring: Guidelines for
Therapeutic Drug Monitoring of CardiovascularDrugs ―Clinical Use of Blood Drug
Concentration Monitoring― (JCS 2015), 24, Life
Science Shuppan, 2016.
11) 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: 2 years from the date of manufacture(The expiration date is printed on the outerpackage.)3