This package insert follows the Pharmaceuticals, Medical devices and Other Therapeutic Products Act of Japan.

In Vitro Diagnostics **Revised: January 2017 (3rd edition) Certification No. 224ADAMX00107000 *Revised: November 2013 (2nd edition) This package insert must be read carefully prior to use.

Arbekacin assay kit antimicrobial activity against staphylococci, (Classification No.: 42929000) arbekacin is expected to be useful for MRSA infection. Clinically significant adverse reactions to arbekacin Nanopia TDM Arbekacin include shock, convulsions, eighth cranial nerve disorders, and acute renal failure. To avoid these General Precautions ＊ adverse reactions, monitoring the blood concentration 1. This product is for in vitro diagnostic use, and of arbekacin after administration is recommended.1) must not be used for any other purposes. Monitoring is also important to promote the 2. Clinicians should make a comprehensive clinical appropriate use of antimicrobial agents based on decision based on assay results in conjunction with PK/PD2). clinical symptoms and other examination results. 3. Please read carefully the "PRECAUTIONS" Assay Principle section, particularly under "Effects on Laboratory 1. Assay Principle Tests" of the package insert of each drug, for When a certain amount of anti-arbekacin antibody information on the influence to the assay result that is added and reacted with a sample, consumption medications administered to the patient have. of the antibody depends on its content in the Please also read carefully the "2) Cross-reactivity," sample. When arbekacin-coated latex is added, under "2. Interfering Substances," in the residual anti-arbekacin antibody reacts with the "Procedural Precautions" section, as well as "2. latex and forms aggregates. Precautions for Assessment" in the "Assessment of Since the extent of aggregation depends on the Assay Results" section, of this package insert. arbekacin concentration in the sample, the 4. This product should be used only as directed in this arbekacin concentration can be determined by package insert. Reliability of results cannot be measuring aggregation as the absorbance. guaranteed if there are any deviations from the instructions in this package insert. Sample (arbekacin) + Anti-arbekacin antibody 5. If the reagent accidentally comes in contact with ────▶ Antigen-antibody reaction eyes and/or mouth, rinse immediately with ample water as first aid, and consult the doctor if Unreacted anti-arbekacin antibody + required. arbekacin-coated latex 6. Carefully read the operating instructions for each ───▶ Aggregation by antigen-antibody reaction type of automated analyzers prior to using this 2. Features product. Parameters for each type of analyzers are 1) Because an anti-arbekacin monoclonal available, and can be requested from SEKISUI antibody is used, this product shows excellent MEDICAL CO., LTD. if required. sensitivity and accuracy. 7. Perform a quality control test prior to assay to 2) Liquid reagents, ready-to-use. ensure accuracy. 3) It can be measured using the automated 8. ABK Antibody Solution 1 contains human-derived analyzers commonly used. components that have been confirmed to be negative for HBs antigens, HIV antibodies, and Procedural Precautions ＊＊ HCV antibodies. However, handle this reagent ＊ 1. Properties of Samples and Sampling Methods with great care in the same manner as the samples, 1) Samples because it is potentially infectious. (1) Serum and plasma (EDTA plasma) may be

used. Description (Kit Components) (2) Do not use samples collected by rapid Component: Ingredients aspiration. ABK Antibody Solution 1: 2) Storage of samples Anti-arbekacin mouse monoclonal (1) After separation of serum (plasma), antibody samples may be stored for up to 7 days in ABK Latex Reagent 2: a refrigerator. If samples cannot be Arbekacin-coated latex measured within 7 days of serum

(plasma) separation, store them at −30C Intended Use or lower and measure them within 14 Measurement of arbekacin in serum or plasma days. Stored samples should be brought

Arbekacin is an antimicrobial agent. to room temperature (15–30C) before It is resistant to various aminoglycoside-inactivating use. enzymes and exhibits strong antimicrobial activity (2) Arbekacin may undergo degradation if against staphylococci, including methicillin-resistant there is a high concentration of a Staphylococcus aureus (MRSA), as well as against β-lactam in the sample. . Because of its strong Perform assay immediately after 1 collection of blood or store the sample 37C Reagent 37C 3) Reagent Measurement frozen. Sample (2) + (1) (Absorbance (3) Samples may be frozen and thawed up to 3.0 μL Approx. 120 μL Approx. ※ I ) twice. 105 μL 5 min 1 min 3) Caution must be exercised, because a 37C Measurement separating agent, etc. in the blood collection 4) (Absorbance tube may affect assay values. Approx. ※ II ) 4) Sampling should be performed after 4 min removing insoluble matter from the sample. Calculation of

Very cloudy specimens should be concentration centrifuged before assay. 2. Interfering substances ※Absorbance I and II: Absorbance at 700 nm 1) Assay results are not affected by free bilirubin Calibration material: Arbekacin Calibrator for (up to 19.4 mg/dL), conjugated bilirubin (up to Nanopia (Manufacture's assigned value) 20.3 mg/dL), hemoglobin (up to 491 mg/dL), ＊＊ formazin turbidity (up to 1410 FTU), or Assessment of Assay Results ＊ rheumatoid factors (up to 500 IU/mL). 1. Reference standard range 2) Cross-reactivity It has been reported that the maximum blood The following table summarizes the concentration of arbekacin is related to its cross-reactivity between arbekacin and other efficacy and the recommended therapeutic range drugs. is 15–20 μg/mL, but there is no clear evidence for Concent- Cross- the upper limit.3 It has also been reported that the Substance ration tested reactivity risk of adverse reactions increases with an (µg/mL) (%) increase in the frequency of abnormally high 15 > 70 maximum and minimum blood concentrations, 11 ND and that the trough value should be < 1–2 μg/mL 3 Kanamycin A 61 1 from the standpoint of protecting renal function. Kanamycin B 61 ND Since the therapeutic concentrations and toxic 60 ND concentrations may overlap, interpretation of 20 –3 assay results should also be based on the patient's 60 –1 clinical findings and other examination results. 150 ND It is recommended that the blood concentration of Teicoplanin 150 0 arbekacin should be measured in a sufficient number of samples for statistical analysis and that 25 2 its therapeutic range should be determined by Vancomycin 100 0 each medical institution. 330 0 2. Precautions for Assessment ND : Not Detectable 1) There may be reactions or interfering reactions 3. Others with non-target substances. If assay results

1) Always use Arbekacin Calibrator for Nanopia appear to be unreliable, repeat the measurement for calibration. (if necessary, after dilution) or try another 2) Precautions for assay range analytical methods. If the arbekacin concentration in the sample 2) This product shows cross-reactivity with exceeds the measurement range, dilute the amikacin. Accurate assay values cannot be sample with arbekacin-free serum, and obtained with samples from patients receiving perform re-measurement. amikacin.

＊＊ Dosage/Administration (Assay Procedure) Performance 1. Preparation of reagents 1. Sensitivity Reagent (1): ABK Antibody Solution 1 is ready 1) Absorbance of standard solution (0.0 µg/mL) to use. is 3200 (Abs. × 10000). Reagent (2): ABK Latex Reagent 2 is ready to 2) The ratio between the absorbance with the use. standard solution (0.0 µg/mL) and that with Before using this product, gently invert the ABK another standard solution (2.0 µg/mL) is 55– Latex Reagent 2 bottle to mix it thoroughly, and 85%. check that there are no bubbles. 2. Accuracy: 80–120 % of the expected assay value 2. Assay Procedure 3. Within-run Reproducibility: This product is compatible with various types of Coefficient of variation ≤ 10 % automated analyzer. An example of the assay (Test methods used for 1.–3. are in-house procedure is indicated below. methods.) 4. Measurement Range5): (On Hitachi 7170 automated analyzer) Minimum detection sensitivity was 0.6μg/mL. Upper measurement limit is 30.0μg/mL. 5. Correlation5) Serum N=70 r=0.997 y=0.98x–0.25 2 Control method: Approved in vitro Packaging diagnostic(fluorescence polarization immuno assay) Name Package 6. Standard Material ABK Antibody 1 × 11 mL Arbekacin (in-house standard material) Nanopia TDM Solution 1 Arbekacin ABK Latex 1 × 12.5 mL Precautions for Use or Handling ＊＊ Reagent 2 1. Precautions for Handling (to Ensure Safety) ＊＊ 1) All samples used in the test should be handled References ＊ as a material possibly infected with HIV, HBV, 1) Package insert of Habekacin Injection 25mg, HCV, or other viruses. To prevent infection, use 75mg, 100mg, and 200mg. disposable gloves and avoid mouth pipetting 2) Kizu J. et al.: Jpn J Chemother, 58(4), 460–465, during the test. 2010. 2) Sodium azide is added as an antiseptic agent in 3) Japanese Society of Chemotherapy, Japanese this product. Therefore, if the reagent comes Society of Therapeutic Drug Monitoring: A in accidentally contact with eyes, mouth or skin, revised edition of guidelines for therapeutic drug rinse immediately with ample water as first aid, monitoring of antimicrobials, 105–113, 2016.1) and consult the doctor if required. 4) Dasgupta A., Dean R., et al.：Am J Clin Pathol. 2. Precautions for use 101（4），456-461（1994） 1) This product should be stored as directed, 5) In house data, SEKISUI MEDICAL CO., LTD. without freezing. Freezing can deteriorate the reagents, which can produce inaccurate results. Contact Therefore, avoid using the reagents which have SEKISUI MEDICAL CO., LTD. been previously frozen. [email protected] 2) Do not use expired reagents. Use of such

reagents cannot guarantee the reliability of ＊＊ Manufacturer measurement values. 3) Do not replenish the reagents. SEKISUI MEDICAL CO., LTD. 1-3, Nihonbashi 2-chome, Chuo-ku, Tokyo, Japan 4) After completion of measurement, this product

should be tightly stoppered and stored in a refrigerator. 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 their containers must be immersed in sodium hypochlorite solution at a concentration of greater than 0.1% for longer than 1 hour or autoclaved at 121ºC for 20 minutes. 2）To prevent infections from spilled samples or solutions containing samples, wipe the spilled area thoroughly with disinfectants such as sodium hypochlorite solution at a concentration of greater than 0.1%. 3) The reagents and treated samples should be discarded as medical waste or industrial waste according to the waste disposal regulations. 4) The reagents should be disposed of in accordance with the Water Pollution Control act or related regulations. 5) Sodium azide has been added as an antiseptic agent in this product . It can react with lead 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.

＊＊ Storage and Shelf Life ＊ 1. Storage temperature: 2–8C 2. Shelf life: 1 year from the date of manufacture (The expiration date is printed on the outer package.)

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