ms_11820796190V1.

Digoxin
Elecsys 2010
MODULAR ANALYTICS E170
11820796 190 100 cobas e 411
cobas e 601
cobas e 602

English ▪ The reaction mixture is aspirated into the measuring cell where the
microparticles are magnetically captured onto the surface of the
Intended use electrode. Unbound substances are then removed with
Immunoassay for the in vitro quantitative determination of digoxin in human ProCell/ProCell M. Application of a voltage to the electrode then induces
serum and plasma. Measurements are used in the diagnosis and treatment chemiluminescent emission which is measured by a photomultiplier.
of digoxin overdose and in monitoring levels of digoxin to ensure proper
therapy. ▪ Results are determined via a calibration curve which is instrument-
specifically generated by 2‑point calibration and a master curve provided
The electrochemiluminescence immunoassay “ECLIA” is intended for use via the reagent barcode.
on Elecsys and cobas e immunoassay analyzers.
Reagents - working solutions
Summary The reagent rackpack is labeled as DIGO.
Digoxin is a widely prescribed steroidal cardio-active glycoside. It acts by
binding and inhibiting the Na+/K+-ATPase which in the end increases the M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL:
intracellular Ca2+ concentration.1,2 This results in a positive inotrope effect
which makes digoxin a beneficial drug for heart failure. It improves the Streptavidin-coated microparticles 0.72 mg/mL; preservative.
strength of myocardial contraction and results in the beneficial effects of R1 Anti-digoxin-Ab~Ru(bpy) (gray cap), 1 bottle, 10 mL:
increased cardiac output, increased Left Ventricular Ejection Fraction, and
decreased Pulmonary Capillary Wedge pressure.3,4 Digoxin therapy also Monoclonal anti-digoxin antibody (mouse) labeled with ruthenium
results in stabilized and slowed ventricular pulse rate.5 complex 15 µg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
Although the availability of crystalline digoxin has permitted the
standardization of drug dosage, therapeutic administration inadvertently, yet R2 Digoxin-derivative~biotin (black cap), 1 bottle, 10 mL:
frequently, results in toxicity. Importantly, symptoms of digoxin toxicity often Biotinylated digoxigenin 1.06 ng/mL; biotin 15 µg/L; phosphate buffer
mimic the cardiac arrhythmias for which the drug was originally prescribed. 100 mmol/L, pH 7.0; preservative.
Digoxin concentrations of 0.9‑2.0 ng/mL in serum or plasma are normally
considered to be therapeutic.6,7 However, later studies observed an Precautions and warnings
increased risk for mortality for digoxin concentrations of 1.2 ng/mL and For in vitro diagnostic use.
higher.8,9 These observations are also reflected in the “ESC Guidelines for Exercise the normal precautions required for handling all laboratory
the diagnosis and treatment of acute and chronic heart failure 2008” which reagents.
recommend a therapeutic concentration range for digoxin of 0.6‑1.2 ng/mL Disposal of all waste material should be in accordance with local guidelines.
10 and other guidelines even recommend limits < 1.0 ng/mL.11
Safety data sheet available for professional user on request.
Toxicity of digoxin may reflect several factors: Avoid foam formation in all reagents and sample types (specimens,
1. The drug has a low therapeutic ratio (i.e. a very small difference exists calibrators and controls).
between therapeutic and toxic tissue levels); Reagent handling
2. Individuals vary in their response to digoxin; The reagents in the kit have been assembled into a ready‑for‑use unit that
3. Absorption of various tablet forms of digoxin may vary over a two-fold cannot be separated.
range;12,13 All information required for correct operation is read in from the respective
4. Susceptibility to digitalis toxicity apparently increases with age mainly reagent barcodes.
associated with renal impairment.4 Storage and stability
In combination with other clinical data, monitoring serum or plasma levels Store at 2‑8 °C.
may provide the physician with useful information to aid in adjusting patient
dosage, and achieving optimal therapeutic effect, while avoiding both Do not freeze.
subtherapeutic and harmful toxic drug levels.14 Store the Elecsys reagent kit upright in order to ensure complete
The Elecsys Digoxin assay employs a competitive test principle using a availability of the microparticles during automatic mixing prior to use.
monoclonal antibody specifically directed against digoxin. Digoxin in the Stability:
sample competes with the added digoxin derivative labeled with biotin for
the binding sites on the ruthenylated antibody-complexa). unopened at 2‑8 °C up to the stated expiration date
a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) ) after opening at 2‑8 °C 12 weeks
Test principle on the analyzers 8 weeks
Competition principle. Total duration of assay: 18 minutes.
Specimen collection and preparation
▪ 1st incubation: By incubating the sample (10 µL) with a digoxin‑specific
ruthenium-labeled antibody, an immunocomplex is formed, the amount Blood samples for digoxin analyses should be collected at trough levels
of which is dependent upon the analyte concentration in the sample. which is just prior to the next drug dose or at least 12 hours, and preferably
24 hours after the previous digoxin dose. Considering a blood elimination
▪ 2nd incubation: After addition of streptavidin-coated microparticles and a half-life of 1.5 days for digoxin, steady state blood concentrations require
digoxin derivative labeled with biotin, the still-vacant sites of the approximately 1 week after initiation of therapy – or longer in case of
ruthenium labeled antibodies become occupied, with formation of an abnormal kidney function.15
antibody-hapten complex. The entire complex becomes bound to the
solid phase via interaction of biotin and streptavidin. Only the specimens listed below were tested and found acceptable.
Serum collected using standard sampling tubes or tubes containing
separating gel.
Li-heparin, K2‑EDTA and K3‑EDTA plasma. Li‑heparin plasma tubes
containing separating gel can be used.

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Digoxin
Criterion: Slope 0.9‑1.1 + intercept within < ± 1x Limit of Blank + coefficient exceptional cases the barcode cannot be read, enter the 15‑digit sequence
of correlation ≥ 0.95. of numbers.
Stable for 7 days at 15‑25 °C, 14 days at 2‑8 °C, 6 months at ‑20 °C. Bring the cooled reagents to approximately 20 °C and place on the reagent
Freeze only once. disk (20 °C) of the analyzer. Avoid foam formation. The system
The sample types listed were tested with a selection of sample collection automatically regulates the temperature of the reagents and the
tubes that were commercially available at the time of testing, i.e. not all opening/closing of the bottles.
available tubes of all manufacturers were tested. Sample collection systems Calibration
from various manufacturers may contain differing materials which could Traceability: This method has been standardized by weighing United States
affect the test results in some cases. When processing samples in primary Pharmacopoeia (USP) digoxin reference material into analyte free human
tubes (sample collection systems), follow the instructions of the tube serum.
manufacturer.
Every Elecsys reagent set has a barcoded label containing specific
Centrifuge samples containing precipitates before performing the assay. information for calibration of the particular reagent lot. The predefined
Heat-inactivated serum can be used. master curve is adapted to the analyzer using the relevant CalSet.
Ensure the samples, calibrators and controls are at 20‑25 °C prior to Calibration frequency: Calibration must be performed once per reagent lot
measurement. using fresh reagent (i.e. not more than 24 hours since the reagent kit was
Due to possible evaporation effects, samples, calibrators and controls on registered on the analyzer). Renewed calibration is recommended as
the analyzers should be analyzed/measured within 2 hours. follows:
Materials provided ▪ after 1 month (28 days) when using the same reagent lot
See “Reagents – working solutions” section for reagents. ▪ after 7 days (when using the same reagent kit on the analyzer)
Materials required (but not provided) ▪ as required: e.g. quality control findings outside the defined limits
▪  11820907322, Digoxin CalSet, 4 x 1.5 mL Quality control
▪  04917049190, PreciControl Cardiac II, for 2 x 2 mL each of For quality control, use PreciControl Cardiac II.
PreciControl Cardiac II 1 and 2 In addition, other suitable control material can be used.
▪  11732277122, Diluent Universal, 2 x 16 mL sample diluent or Controls for the various concentration ranges should be run individually at
least once every 24 hours when the test is in use, once per reagent kit, and
 03183971122, Diluent Universal, 2 x 36 mL sample diluent following each calibration.
▪ General laboratory equipment The control intervals and limits should be adapted to each laboratory’s
▪ Elecsys 2010, MODULAR ANALYTICS E170 or cobas e analyzer individual requirements. Values obtained should fall within the defined
Accessories for Elecsys 2010 and cobas e 411 analyzers: limits. Each laboratory should establish corrective measures to be taken if
values fall outside the defined limits.
▪  11662988122, ProCell, 6 x 380 mL system buffer Follow the applicable government regulations and local guidelines for
▪  11662970122, CleanCell, 6 x 380 mL measuring cell cleaning quality control.
solution
Calculation
▪  11930346122, Elecsys SysWash, 1 x 500 mL washwater additive The analyzer automatically calculates the analyte concentration of each
▪  11933159001, Adapter for SysClean sample (either in nmol/L or ng/mL).
▪  11706802001, Elecsys 2010 AssayCup, 60 x 60 reaction vessels Conversion factors: nmol/L x 0.78 = ng/mL
▪  11706799001, Elecsys 2010 AssayTip, 30 x 120 pipette tips ng/mL x 1.28 = nmol/L
Accessories for MODULAR ANALYTICS E170, cobas e 601 and
cobas e 602 analyzers: Limitations - interference
▪  04880340190, ProCell M, 2 x 2 L system buffer The assay is unaffected by icterus (bilirubin ≤ 1129 µmol/L or ≤ 66 mg/dL),
hemolysis (Hb ≤ 0.621 mmol/L or ≤ 1.0 g/dL), lipemia (Intralipid
▪  04880293190, CleanCell M, 2 x 2 L measuring cell cleaning ≤ 1500 mg/dL) and biotin (≤ 409 nmol/L or ≤ 100 ng/mL).
solution
Criterion: Recovery within ± 0.08 ng/mL (± 0.10 nmol/L) for digoxin
▪  03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and concentrations ≤ 0.8 ng/mL (≤ 1.02 nmol/L) or ± 10 % for concentrations
CleanCell M before use > 0.8‑4.0 ng/mL (> 1.02‑5.12 nmol/L) or ± 12 % for concentrations
▪  03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run > 4.0 ng/mL (> 5.12 nmol/L).
finalization and rinsing during reagent change Samples should not be taken from patients receiving therapy with high
▪  03004899190, PreClean M, 5 x 600 mL detection cleaning solution biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin
administration.
▪  12102137001, AssayTip/AssayCup Combimagazine M,
48 magazines x 84 reaction vessels or pipette tips, waste bags No interference was observed from rheumatoid factors up to a
concentration of 1630 IU/mL.
▪  03023150001, WasteLiner, waste bags In vitro tests were performed on a panel of commonly used
▪  03027651001, SysClean Adapter M pharmaceuticals. While 34 of these showed no interference with the assay,
Accessories for all analyzers: uzara, nabumetone, hydrocortisone, pentoxifylline and canrenone were
identified to cause falsely elevated digoxin values at concentrations of the
▪  11298500316, ISE Cleaning Solution/Elecsys SysClean, recommended daily dose.
5 x 100 mL system cleaning solution
Spironolactone causes elevated digoxin results above (drug) levels of
Assay 10000 ng/mL. Canrenone causes elevated digoxin results above (drug)
For optimum performance of the assay follow the directions given in this levels of 80000 ng/mL.
document for the analyzer concerned. Refer to the appropriate operator’s Digoxin-like immunoreactive substances (DLIS) have been identified in
manual for analyzer‑specific assay instructions. blood from patients in renal failure, liver failure, and pregnant women in
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers: their third trimester. Studies have shown that the presence of DLIS in a
PreClean M solution is necessary. sample can result in a false elevation of digoxin when assayed by
Resuspension of the microparticles takes place automatically prior to use. commercially available immunoassays.16,17,18
Read in the test‑specific parameters via the reagent barcode. If in As stated by the manufacturers of digitalis antidotes, the therapeutic
antibody fragments against digitalis (e.g. DigiFab, DigiBind) will interfere

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Digoxin
with digitalis immunoassay measurements.19 Therefore, the manufacturer of Institute): 2 runs per day in duplication each for 21 days (n = 84). The
DigiFab recommends to obtain samples for determination of digoxin following results were obtained:
concentration prior to antidote administration.19 As a consequence Elecsys
Digoxin concentrations may be falsely elevated if measured in the presence Elecsys 2010 and cobas e 411 analyzers
of the antidote until the Fab fragments are eliminated from the body.19 Repeatability Intermediate
In rare cases, interference due to extremely high titers of antibodies to precision
analyte‑specific antibodies, streptavidin or ruthenium can occur. These
effects are minimized by suitable test design. Sample Mean SD CV SD CV
For diagnostic purposes, the results should always be assessed in nmol/L nmol/L % nmol/L %
conjunction with the patient’s medical history, clinical examination and other Human serum 1 0.724 0.025 3.4 0.046 6.4
findings.
Human serum 2 1.39 0.035 2.5 0.080 5.8
Limits and ranges
Measuring range Human serum 3 2.37 0.049 2.1 0.106 4.5
0.2‑5.0 ng/mL or 0.26‑6.4 nmol/L (defined by the Limit of Detection and the Human serum 4 3.05 0.071 2.3 0.117 3.8
maximum of the master curve). Values below the Limit of Detection are Human serum 5 5.98 0.152 2.5 0.382 6.4
reported as < 0.2 ng/mL or < 0.26 nmol/L. Values above the measuring
range are reported as > 5.0 ng/mL or > 6.4 nmol/L (or up to 10.0 ng/mL or PCb) CARDII1 1.54 0.045 2.9 0.066 4.3
12.8 nmol/L for 2-fold diluted samples). PC CARDII2 3.51 0.131 3.7 0.143 4.1
Lower limits of measurement
b) PC = PreciControl
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank = 0.15 ng/mL (0.19 nmol/L) Elecsys 2010 and cobas e 411 analyzers
Limit of Detection = 0.2 ng/mL (0.26 nmol/L) Repeatability Intermediate
Limit of Quantitation = 0.4 ng/mL (0.51 nmol/L) with a total allowable error precision
of ≤ 20 %
Sample Mean SD CV SD CV
The Limit of Blank, Limit of Detection and Limit of Quantitation were ng/mL ng/mL % ng/mL %
determined in accordance with the CLSI (Clinical and Laboratory Standards
Institute) EP17‑A2 requirements. Human serum 1 0.565 0.019 3.4 0.036 6.4
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of Human serum 2 1.09 0.027 2.5 0.063 5.8
analyte‑free samples over several independent series. The Limit of Blank
corresponds to the concentration below which analyte‑free samples are Human serum 3 1.85 0.039 2.1 0.083 4.5
found with a probability of 95 %. Human serum 4 2.38 0.055 2.3 0.092 3.8
The Limit of Detection is determined based on the Limit of Blank and the Human serum 5 4.67 0.119 2.5 0.299 6.4
standard deviation of low concentration samples. The Limit of Detection
corresponds to the lowest analyte concentration which can be detected PC CARDII1 1.20 0.035 2.9 0.051 4.3
(value above the Limit of Blank with a probability of 95 %).
PC CARDII2 2.74 0.102 3.7 0.111 4.1
The Limit of Quantitation is defined as the lowest amount of analyte in a
sample that can be accurately quantitated with a total allowable error of MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers
≤ 20 %.
Repeatability Intermediate
Dilution
precision
Samples with digoxin concentrations above the measuring range can be
diluted with Diluent Universal. The recommended dilution is 1:2 (either Sample Mean SD CV SD CV
automatically by the MODULAR ANALYTICS E170, Elecsys 2010 or nmol/L nmol/L % nmol/L %
cobas e analyzers or manually). The concentration of the diluted sample
must be > 2.5 ng/mL or > 3.2 nmol/L. Human serum 1 0.712 0.045 6.3 0.058 8.2
After manual dilution, multiply the result by the dilution factor. Human serum 2 1.36 0.038 2.8 0.058 4.3
After dilution by the analyzers, the MODULAR ANALYTICS E170, Human serum 3 2.33 0.058 2.5 0.084 3.6
Elecsys 2010 and cobas e software automatically takes the dilution into
account when calculating the sample concentration. Human serum 4 2.94 0.069 2.4 0.111 3.8
Expected values Human serum 5 5.49 0.147 2.7 0.276 5.0
The recommended therapeutic range for digoxin is 0.6‑1.2 ng/mL PC CARDII1 1.55 0.037 2.4 0.056 3.6
(0.77‑1.5 nmol/L) (ESC Guideline 200810) or even 0.5‑1.0 ng/mL
(0.64‑1.3 nmol/L).20 Particularly the upper end of the therapeutic range is PC CARDII2 3.50 0.047 1.3 0.082 2.3
controversial and concentrations up to 2.0 ng/mL (2.6 nmol/L) may still be
applied.6,7 Concentrations > 2.0 ng/mL are generally considered toxic.21 MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers
Some overlap of toxic and non‑toxic values has been reported.22 Repeatability Intermediate
Therefore, clinical diagnosis should be based on clinical and laboratory precision
data. Each laboratory should establish an acceptable reporting format and
identify procedures for the reporting of abnormal results. Sample Mean SD CV SD CV
Each laboratory should investigate the transferability of the expected values ng/mL ng/mL % ng/mL %
to its own patient population and if necessary determine its own reference Human serum 1 0.556 0.035 6.3 0.046 8.2
ranges.
Human serum 2 1.07 0.030 2.8 0.045 4.3
Specific performance data
Representative performance data on the analyzers are given below. Human serum 3 1.82 0.045 2.5 0.066 3.6
Results obtained in individual laboratories may differ. Human serum 4 2.29 0.054 2.4 0.087 3.8
Precision Human serum 5 4.29 0.115 2.7 0.216 5.0
Precision was determined using Elecsys reagents, samples and controls in PC CARDII1 1.21 0.029 2.4 0.044 3.6
a protocol (EP5‑A3) of the CLSI (Clinical and Laboratory Standards

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Digoxin
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers 9 Adams KF, Patterson JH, Gattis WA, et al. Relationship of Serum
Digoxin Concentration to Mortality and Morbidity in Women in the
Repeatability Intermediate Digitalis Investigation Group Trail. J Am Coll Cardiology
precision 2005;46(3):497-504.
Sample Mean SD CV SD CV 10 Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the
ng/mL ng/mL % ng/mL % diagnosis and treatment of acute and chronic heart failure 2008: the
Task Force for the Diagnosis and Treatment of Acute and Chronic
PC CARDII2 2.74 0.037 1.3 0.064 2.3 Heart Failure 2008 of the European Society of Cardiology. Developed
Analytical specificity in collaboration with the Heart Failure Association of the ESC (HFA)
and endorsed by the European Society of Intensive Care Medicine
For the Co-analytes tested, the following relative Co-analyte reactivities (ESICM). Eur Heart J 2008;29:2388-2442.
were found: 11 Goldberger ZD, Goldberger AL Therapeutic Ranges of Serum Digoxin
Concentrations in Patients with Heart Failure. Am J Cardiol
Co-analyte Concentration Relative Co-analyte 2012;109:1818-1821.
ED50 reactivity
12 Lindenbaum J, Mellow MH, Blackstone MO, et al. Variation in Biologic
ng/mL % Availability of Digoxin from Four Preparations. New Engl J Med
α-acetyldigoxin 1.18 77.9 1971;285:1344-1347.
β-acetyldigoxin 1.09 84.4 13 Lindenbaum J, Butler VP Jr., Murphy JE, et al. Correlation of Digoxin-
Tablet Dissolution Rate with Biological Availability. Lancet
β-methyldigoxin 1.05 87.9 1973;1:1215-1217.
Lanatoside C 1.31 65.2 14 Butler VP Jr., Lindenbaum J. Serum Digitalis Measurements in the
Deslanoside 1.08 85.6 Assessment of Digitalis Resistance and Sensitivity. Am J Med
1975;58:460-469.
Digoxigenin-bis- 0.853 108 15 Frendl G, Sodickson AC, Chung MK, et al. 2014 AATS guidelines for
digitoxoside the prevention and management of perioperative atrial fibrillation and
Digoxigenin-mono- 0.603 141 flutter for thoracic surgical procedures. J Thorac cardiovasc Surg
digitoxoside 2014;148(3):e153-93.
16 Keys PW, Stafford RW. In: Taylor WJ, Finn AL, eds. Individualizing
For the substances tested, the following cross-reactivities were found: Drug Therapy: Practical Applications of Drug Monitoring. New York,
Gross, Townsend, Frank, Inc; 1981; vol 3:1-21.
Substances Concentration tested Cross-reactivity
17 Valdes R Jr. Endogenous digoxin-like immunoreactive factors: impact
ng/mL % on digoxin measurements and potential physiological implications. Clin
Digitoxin 250 0.522 Chem 1985;31(9):1525-1532.
Digitoxigenin 250 0.529 18 Valdiva R, Hornig Y, Gross S, et al. Digoxin-like Immunoreactive Factor
Cross-reactivity in the CEDIA Digoxin R Assay on the RA-1000. Clin
Digoxigenin 6.00 31.3 Chem 1990;36(6):1111.
Dihydrodigoxin 1000 0.201 19 DigiFab® Package Insert. P12011D (1-Aug-2014). BTG International
K-strophanthine 1250 0.137 Inc.
20 Terra SG, Washam JB, Dunham GD, et al. Therapeutic Range of
No significant cross-reactivity (< 0.01 %) was found for the following Digoxin’s Efficacy in Heart Failure: What Is The Evidence?
substances (tested concentration 5000 ng/mL): Pharmacotherapy 1999;19(10):1123-1126.
Cortisol, prednisone, β‑estradiol, d‑aldosterone, DHEA, dexamethasone, 21 Matzuk MM, Shlomchik M, Shaw LM. Therapeutic Drug Monitoring
furosemide, sulthiame, quinidine (free base) and oleandrin. For 1991;13:215-219.
testosterone and ouabain a cross-reactivity of < 0.1 % was found at
5000 ng/mL. For progesterone a cross-reactivity of < 0.05 % was found at 22 Beller GA, Smith TW, Abelmann WH, et al. Digitalis Intoxication: A
5000 ng/mL. Prospective Clinical Study with Serum Level Correlations. New Engl J
Med 1971;284:989-997.
References
1 Hauptmann PJ, Kelly RA Digitalis. Circulation 1999;99:1265-1270. For further information, please refer to the appropriate operator’s manual for
the analyzer concerned, the respective application sheets, the product
2 Katz A, Lifshitz Y, Bab-Dinitz E, et al. Selectivity of Digitalis Glycosides information and the Method Sheets of all necessary components (if
for Isoforms of Human Na,K-ATPase. J Biol Chem 2010 Jun;285(25) available in your country).
19582-19592. A point (period/stop) is always used in this Method Sheet as the decimal
3 Eichhorn EJ, Gheorghiade M Digoxin. Progress Cardiovasc Diseases separator to mark the border between the integral and the fractional parts of
2002 Jan/Feb;44(4):251-266. a decimal numeral. Separators for thousands are not used.
4 Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary Use of Symbols
Digoxin in the Management of Cardiovascular Disorders. Circulation Roche Diagnostics uses the following symbols and signs in addition to
2006;113:2556-2564. those listed in the ISO 15223‑1 standard.
5 Hoffman BF, Bigger JT Jr. In: Gilman AG, Goodman LS, Gilman A, eds.
The Pharmacological Basis of Therapeutics. 6th ed. New York, NY: Contents of kit
MacMillan; 1980:729-760. Analyzers/Instruments on which reagents can be used
6 Oellerich M. Pharmaka (Drug monitoring). In: Thomas L (ed.). Labor
und Diagnose, TH-Books, Frankfurt, 5. edition, 1998:1174. Englisch: Reagent
Clinical Laboratory. 1st English Edition 1998:1151. Calibrator
7 Jortani SA, Valdes R Jr. Digoxin and Its Related Endogenous Factors. Volume after reconstitution or mixing
Critical Reviews Clin Lab Sci 1997;34(3):225-274.
8 Rathore SS, Curtis JP, Wang Y, et al. Association of Serum Digoxin GTIN Global Trade Item Number
Concentration and Outcome in Patients with Heart Failure. JAMA 2003
Feb;289(7):871-878.

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Digoxin
COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
Fresenius Kabi AB.
All other product names and trademarks are the property of their respective owners.
Additions, deletions or changes are indicated by a change bar in the margin.
© 2015, Roche Diagnostics

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