YAO2016

Critical Reviews in Clinical Laboratory Sciences
ISSN: 1040-8363 (Print) 1549-781X (Online) Journal homepage: http://www.tandfonline.com/loi/ilab20
FDA-approved drugs that interfere with laboratory

tests: A systematic search of U.S. drug labels
Hui Yao, Elizabeth R. Rayburn, Qiang Shi, Liang Gao, Wenjie Hu & Haibo Li
To cite this article: Hui Yao, Elizabeth R. Rayburn, Qiang Shi, Liang Gao, Wenjie Hu &
Haibo Li (2016): FDA-approved drugs that interfere with laboratory tests: A systematic
search of U.S. drug labels, Critical Reviews in Clinical Laboratory Sciences, DOI:
10.1080/10408363.2016.1191425
To link to this article: http://dx.doi.org/10.1080/10408363.2016.1191425
Accepted author version posted online: 18

May 2016.
Published online: 18 May 2016.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ilab20
Download by: [University of Nebraska, Lincoln] Date: 20 May 2016, At: 03:23
FDA-approved drugs that interfere with laboratory tests: A systematic search of
U.S. drug labels
Hui Yao1*, Elizabeth R. Rayburn2*, Qiang Shi3, Liang Gao1, Wenjie Hu1, Haibo Li1
1
Department of Clinical Laboratory Medicine, Nantong Maternity and Child Health
Hospital, Nantong, China

Downloaded by [University of Nebraska, Lincoln] at 03:23 20 May 2016
2
CLIA Laboratory Director (various laboratories), Birmingham, AL, USA
D
3
Division of Systems Biology, National Center for Toxicological Research, U.S. Food
and Drug Administration, Jefferson, AR, USA

TE
EP
*
These authors contributed equally to the manuscript
C
AC
Address correspondence to: Haibo Li, Ph.D., Department of Reproductive Medicine,
Nantong Maternity and Child Health Hospital, Nantong, China. Email
ntlihaibo2015@163.com
ST
JU
Keywords: Drug-related laboratory test interference (DLTI), prescription drugs, FDA
labels, DailyMed
Referees Adel Ismail, Consultant in Clinical Biochemistry and Chemical

Endocrinology (retired), Tanglewood, Chevet Lane, Wakefield, West Yorkshire, UK;
Dr. Theo Rispens, Sanquin Research, Amsterdam, The Netherlands; Dr. Daniel
Amsterdam, Professor, Departments of Microbiology, Pathology, and Medicine,
School of Medicine, University at Buffalo, Buffalo, NY, USA.
Received 22 December 2015
Revised 08 May 2016
Accepted 16 May 2016
Published online
Abbreviations and Glossary
AACC, American Association for Clinical Chemistry, a global organization that is
dedicated to improving the clinical laboratory sciences and promotes their application
for healthcare
ACE, angiotensin-converting enzyme
D
ALT, alanine transaminase
AST, aspartate transaminase TE

EP
ADME, absorption, distribution, metabolism and excretion
CBC, complete blood cell count, a common laboratory analysis performed to

C
determine the numbers erythrocytes, leukocytes and thrombocytes, as well as the

AC
hemoglobin and hematocrit concentrations and mean corpuscular volume
DailyMed, a U.S.-sponsored online database of drug labels that is free to use

ST
DLTI, drug-related laboratory test interference or drug/laboratory test interactions, the
interference of xenobiotic substances with laboratory assays

JU
EMR, electronic medical records

FDA, U.S. Food and Drug Administration, the U.S. entity responsible for regulating
new foods and health-related products

IFCC, International Federation of Clinical Chemistry and Laboratory Medicine
IQCP, Individual Quality Control Plan

LDH, lactate dehydrogenase
OTC, over-the-counter, referring to health-related products that are sold to consumers
but have not been FDA-approved
PT/INR, prothrombin time/international normalized ratio
Abstract
Drug-related laboratory test interference or drug/laboratory test interactions (DLTI) is
a major source of laboratory errors. DLTI is of concern with regard to both the clinical
diagnosis and the monitoring of patients. Although there have been numerous reports
D
about specific drugs that interfere with laboratory tests, there has not been a recent
TE
review on the topic. We herein provide a review of the known DLTI of U.S.
FDA-approved drugs based on a systematic search of DailyMed, a website containing

EP
the labels of U.S. FDA-approved drugs. The labels for all human single-ingredient
C
prescription drugs included in the database (1,368) were searched using stemmed
AC
keywords, and were manually reviewed for their relevance to DLTI. A total of 134
labels were positive, which indicated that the drug interferes with at least one clinical
laboratory test. Antibacterial agents, psychotropic drugs, and contrast media are the
ST
classes of drugs most likely to lead to DLTI. Urine was the clinical sample most
JU
frequently affected by DLTI. The FDA drug label is a source of information for
studies of DLTI, although information is still lacking for most drugs, and additional
improvements are needed for many of the existing records. Medical professionals,
clinicians and laboratory staff should keep these possible interactions in mind when
interpreting the results of laboratory tests, and should ensure that they obtain a
complete and accurate record of all drugs being used by patients in order to anticipate
potential DLTI. The development of a reporting system to address potential DLTI is
warranted.
Introduction
The reliance of modern medicine on laboratory testing
The fundamental task of a clinical laboratory is to provide accurate and precise

results for the diagnosis of a disease, determination of its prognosis, indications of
D
changes in a patient’s condition over time, information regarding the response to
TE
treatment, and/or evidence of patient compliance with the treatment. There are
approximately 4,000 different laboratory tests that have been developed, about a
EP
quarter of which have payment rates set in the Medicare Clinical Laboratory Fee
C
Schedule (1). It has been estimated that 70% of the medical decisions made in the U.S.
AC
are based on the findings of clinical laboratory tests (2). Although this high percentage
includes decisions made based on imaging and pathology studies, more than two
billion dollars were reimbursed by Medicare in 2006 for just four clinical chemistry
ST
tests (complete blood count, complete CBC panel with differential WBC counts;
JU
comprehensive metabolic panel[albumin, blood urea nitrogen, calcium, CO2, chloride,
creatinine, glucose, potassium, sodium, total bilirubin, total protein, and liver enzyme
levels (AST, ALP, AST)]; thyroid stimulating hormone assay; and routine lipid panel
[total cholesterol, LDL, HDL, and triglycerides]: HCPCS# 85025, 80052, 84443, and
80061, respectively (3)). Given the increasing demand for individualized medicine by
patients, laboratory testing will likely play an increasingly important role in clinical
decision-making.
This increasing use of and reliance on laboratory testing has been due to and has
led to the development of a wide variety of technologies, ranging from simple test
strip/dipstick immunoassays to genetic sequencing and microarrays. As the
complexity of the tests (and their interpretation) and the number of samples being
tested increases, the potential risk of interference with these tests by commonly-used
substances will increase. The purpose of this review is to provide an updated
D
summary of the FDA-approved (FDA, U.S. Food and Drug Administration),
TE
single-ingredient drugs that can interfere with the performance, outcome or
interpretation of laboratory tests. We also discuss the existing reporting of these

EP
findings, and suggest ways to improve the identification and understanding of
C
drug-related laboratory test interference (DLTI).

AC
The implications of drug-related laboratory test interference
Although new instruments and methods are constantly being developed to

ST
provide more accurate results with greater sensitivity, there is a margin of error for all
JU
laboratory tests, and the testing may be affected by a number of factors. One potential
source of error is the drugs that the patients are taking. Many drugs lead to spurious
results for clinical laboratory tests by interfering with the assays. If the fact that the
test results are incorrect is missed, this may mislead the medical staff and potentially
result in harm to patients. Such harm may result from a missed diagnosis, an incorrect
diagnosis, improper prognostic prediction, an incorrect evaluation of the response to
treatment, or an incorrect evaluation of a patient’s drug use or compliance with the
prescribed treatment. While the potential risk may be minimal in some cases and
possibly lead only to an additional test being performed, there is a chance for some
interference to lead to a lost opportunity for treatment or to treatment with an
inappropriate therapy that would potentially lead to morbidity or death.
Although the rates of DLTI are currently unclear, there have been some large
studies performed to examine the rates for immunoassays because their use of
D
antibodies is inherently associated with a risk of cross-reactivity with endogenous
TE
immunoglobulins and heterophilic antibodies. The reported rates of DLTI for
immunoassays ranged from 0.4-4.0% (4). Although a accuracy rate of 99.5% is

EP
considered to be good for most assays, this rate still means that there are thousands or
C
even millions (depending on the assay) of inaccurate results obtained every year.
AC
Methods such as the precipitation of heterophilic antibodies prior to testing are being
developed to further decrease this rate (5), but these are not yet widely used and they
will add to the cost and complexity of these tests.

ST
There are numerous requirements for method development that are considered by
JU
the instrument and reagent manufacturers, government regulatory bodies, and
individual laboratories that have been implemented specifically to avoid the risk of
DLTI. The FDA has set forth recommendations for testing for interference during the
development of devices/instruments and new testing methods by manufacturers that
are largely based on the target analyte(s), the type of test, and the substance(s) being
tested (blood, urine, histology, etc.) (i.e., sections 513 and 515 of the FD&C Act; 21
U.S.C. 360c and 360e) (6). The findings of such testing are included in the user
manual or instructions for use of the instruments/reagents. These can provide useful
information to the laboratory staff, but are often not reflective of the actual conditions
in the laboratory. There may be a different spectrum of interference due to differences
in the instrument performance in the laboratory (e.g. effects of temperature and
humidity), differences in the patient population (e.g. different ethnicity, underlying

diseases, seasonality or timing of the sample collection), and differences in the skill
D
level of the laboratory staff. Ideally, interference testing should be performed by both
the instrument/reagent provider and by the end user.

TE
Most method validation protocols, especially for high-complexity testing, include
EP
steps to search for interference by several of the most commonly-used
C
over-the-counter (OTC) and prescription drugs and drugs with structures that are
AC
similar to that of the target analyte. However, it is impossible for manufacturers and
laboratories developing methods to identify all potential sources of cross-reactivity or
drug-related interference during method validation. In addition, while validation is

ST
now required for all laboratory-developed tests, there are no detailed requirements for
JU
interference testing, only that the test be specific and precise (7). Thus, efforts must be
made to continue monitoring for interference and to record cases of suspected
interference as they arise, because not all can be identified or examined during the
initial method development and validation.

Existing knowledge about DLTI
Drugs can impact the results of laboratory tests in several ways. One is by
altering the pharmacology/ADME (absorption, distribution, metabolism and excretion)
of other drugs. Another is by altering the biological sample being tested (e.g.
hemolysis in blood). Some drugs also interfere directly with the test itself by reacting
with the test reagents. This review will focus on the latter two mechanisms of drug
interference with laboratory tests.

Although there have been numerous reports about drug-related interference with
D
laboratory tests, most of them have focused on individual drugs, methods, or
TE
instruments (8-14). There have been only a few reviews that have attempted to
provide an overall summary of the variety of data presented in these reports. The
EP
authority in the field has long been Dr. Donald Young, who published several reviews
C
(including three in the 1970s and another in 1997) about the impact of drugs on
AC
laboratory tests (14a, 15-17). He additionally participated in the launch with the
American Association for Clinical Chemistry (AACC) of a large online database in
2004 that was based on several of his previously published books; this database is still
ST
active and includes detailed information about various DLTI (18). Although Dr.
JU
Young’s work laid the foundation, additional reviews and continuous reporting of
potential DLTI are needed.
Aims of this review
To our knowledge, no comprehensive profile of drug-related laboratory test

interference has been reported in more than a decade. Therefore, in the present review,
we provide an updated and comprehensive overview of the DLTI associated with
single-ingredient U.S. Food and Drug Administration (FDA)-approved drugs.
According to the updated guidelines issued by the U.S. FDA in October 2011, the
information about any known drug interference with clinical laboratory tests must be
briefly noted in the WARNINGS AND PRECAUTIONS section of the drug label (19).
In the present study, we reviewed and analyzed all of the FDA-approved human
prescription drug labels deposited in DailyMed (https://dailymed.nlm.nih.gov
D
[last accessed 15 May 2016), which contains more than 85% of all U.S. drug labels,
TE
and analyzed the information related to DLTI, including the drug classification,
laboratory assay classification, and the mechanism by which the drug interferes with
EP
the assay (if known).
C
AC
Methods
The inclusion and exclusion criteria for the drugs evaluated in the study
Nearly all U.S. drug labels are deposited in the federal DailyMed website. A list
ST
of drugs for subsequent study was developed based on a search of the DailyMed
JU
website performed on April 22, 2015. The recorded information included the product
name, product generic name, market category, route(s) of administration, dosage
form(s), and the last time the label was updated.
We examined only the drugs used for humans (drugs intended for animal use
were not considered). Only FDA-approved prescription drug labels were included for
review. Over-the-counter (OTC) drugs were excluded from the database because
DLTI-related information was generally not available in their labels. The drugs
containing multiple active ingredients were also excluded because this made it
difficult to evaluate the effects of a specific compound. When there were repeated
labels for the same drug from different companies, or when there were labels that had
been updated at different times, only the latest label was used for the subsequent
review.
D
Searching with keywords
TE
The labels for all drugs included in the study were downloaded from DailyMed in
the PDF format. A hyperlink that linked the drug in the database to the PDF document
EP
was established to conveniently access the information. For every PDF document,
C
stemmed keywords were used to search the label contents for relevant information;
AC
these keywords included “analy*”, “artifact*”, “assay”, “clinic*”, “determine*”,
“erro*”, “false”, “interfer*”, “interact*”, “lab*”, “spuriou*” and “test” to cover the
potentially useful information to the best extent possible. Every stemmed keyword
ST
represented several words potentially related to DLTI (e.g. “analy*” was used to find
JU
information related to “analyse(d)(s)” “analyze(d)(s)”, “analysis”, “analyte”, and
“analytical”).
The PDF documents were manually searched independently by two authors using
these keywords, and the described relevance to DLTI was copied and pasted into an
Excel database. If there were differences in the descriptions obtained by the two
authors, they were resolved by discussion with another author, and the group opinion
was used for the statistical analyses. Only the labels with a confirmed description
related to DLTI were included in the study, such as “High urine concentrations of
ampicillin may result in false-positive reactions when testing for the presence of
glucose in urine using the CLINITEST, Benedict’s Solution, or Fehling’s Solution.”, or
“Nitrates and nitrites may interfere with the Zlatkis-Zak color reaction, causing
falsely low readings in serum cholesterol determinations.”

D
Analysis of the findings
TE
For the drugs with positive findings in the FDA labels regarding interference with
laboratory tests, we performed further analyses. The positive drugs were classified by
EP
their applications according to the principle category in the US National Library of
C
Medicine (http://druginfo.nlm.nih.gov/drugportal [last accessed 15 May 2016]). The

AC
anti-infective agents were defined as all agents targeting microbes other than bacteria
(e.g. antiviral, anti-fungal, anti-malarial, and anti-protozoal agents). Antidepressant,
anti-Parkinson and antipsychotic agents were all listed in the category of psychotropic
ST
drugs, because they result in changes in brain function and result in alterations in
JU
perception, mood, or consciousness. The cardiovascular agents included all drugs
indicated for problems with the circulatory system (e.g. anti-hypertensive drugs,
beta-blockers, antiarrhythmic drugs).

Results
The drugs included in this study
As of April 22, 2015, a total of 65,536 labels had been deposited in DailyMed. A
total of 29,145 labels were excluded for 24,859 OTC drugs that did not include
relevant information. Another 814 drug labels for drugs used only in animals and
11,199 labels for non-FDA-approved drugs were also excluded from further analysis.
A total of 22,724 human drug labels were kept after deleting the labels for
medicinal foods, medical devices, dietary supplements, cosmetics, bulk ingredients,
D
diagnostic kits, etc. For the drugs with multiple labels from different manufacturers,
TE
different effective doses, and/or different routes of administration and/or dosage forms,
only the latest label was used for the analysis. The final list of human
EP
single-ingredient prescription drugs included 1,368 drug labels, which were all
C
examined for information about interference with laboratory tests.

AC
The profile of DLTI in the FDA-approved single-ingredient prescription drugs
The most prominent finding of this study was that only 12.35% (169/1,368) of the
ST
FDA labels for human single-ingredient prescription drugs provided explicit

JU
information related to DLTI. Among these, 134 labels clearly indicated that the drug
interferes with laboratory tests (shown in Table 1 (urine-based assays) and Table 2
(blood-based assays)), 31 labels indicated that the drug did not interfere with
laboratory tests, and only four labels noted that there was no information regarding
laboratory test interference for the drug. There is no information related to DLTI
available in the labels for most of the FDA-approved prescription drugs. This
indicates that studies of DLTI have been lacking for most drugs.
The drugs most likely to interfere with laboratory tests
Anti-bacterial agents. Based on the drug labels, anti-bacterial agents are the drugs
most likely to interfere with laboratory tests. Most of the reported interfering
anti-bacterial agents were cephalosporins, and the clinical laboratory tests most
susceptible to interference by the cephalosporins were urine glucose and ketone tests.
D
The administration of cephalosporins may result in a false positive reaction for
TE
glucose in the urine using the Clinitest® (Bayer, Ecatepec, Mexico), Benedict's
solution, or Fehling's solution. The Clinitest® reagent tablets and Benedict's and
EP
Fehling’s solutions contain blue copper (II) ions (Cu2+), which are reduced to copper
C
(I) ions (Cu+) by sugars and reducing substances (20-22). These are precipitated as
AC
red copper (I) oxide, which is insoluble in water, and can be used to assess the level of
glucose/ketones in urine. Several cephalosporins also reduce the copper ions, leading
to false positive results. Fortunately, these three methods are seldom used in clinical
ST
laboratories today because of the development of newer methods and automated

JU
assays. In addition, almost all of the labels for these drugs recommend that glucose
testing should be based on enzymatic glucose oxidase or hexokinase reactions to
avoid false positive findings. However, Benedict's and Fehling's solutions may still be
used for glucose tests in some rapid test strips sold in pharmacies or supermarkets,
and consumers may not understand the implications of such DLTI. Of interest, many
cephalosporins also lead to false positive findings for the direct Coombs test (to detect
immune-mediated hemolytic anemia), findings which could potentially lead to an
incorrect diagnosis.
Some anti-bacterial agents can also interfere with the detection of the clotting
time. Both telavancin and daptomycin lead to falsely prolonged/elevated PT/INR
(prothrombin time/international normalized ratio) findings, which could lead to an
unnecessary and potentially dangerous decrease in the dose of anticoagulant being

given. These agents appear to act via distinct mechanisms, with daptomycin
D
interacting with the recombinant prothrombin reagent, and telavancin interacting with
TE
the surface of the phospholipids included in the test kits, and preventing the
coagulation complexes from assembling (23, 24).

EP
C
Psychotropic drugs The psychotropic drugs were found to be the second most likely
AC
agents to interfere with laboratory tests. These agents include antidepressants,
antidyskinesia agents and antipsychotic agents. The determination of whether a
patient is positive for a drug such as phencyclidine, amphetamine or benzodiazepines

ST
may be affected by treatment with other psychotropic drugs. This interference is

JU
logical, because the structures of phencyclidine, amphetamine, and benzodiazepines
drugs are similar to those of the other psychotropic drugs or their metabolites. This
potential for interference needs to be kept in mind by laboratory personnel and/or
clinicians (or by the agency performing employee drug testing), because it may lead
to incorrect conclusions regarding compliance.

Of note, these drugs also have some other forms of interference that occur via an
unknown mechanism. For example, some of these drugs have been reported to lead to
false positive results on pregnancy tests, and information is not available in the drug
label (or in the literature) to explain the reason for this interference. Most pregnancy
tests are carried out using immunoassays based on human chorionic gonadotropin
(HCG) and anti-HCG antibody binding (25). Theoretically, this is the most specific
assay method currently used in clinical laboratories, so it is difficult to explain why

some psychotropic drugs would cause interference.
D
TE
Contrast media According to the FDA labels, contrast media are another major class
of drugs that interfere with laboratory tests. A medical contrast medium is a substance
EP
used to enhance the contrast of structures or fluids within the body during medical
C
imaging. Organic iodine molecules are the most common type of contrast media used
AC
for enhancement in X-ray-based imaging methods, whereas gadolinium contrast
agents are typically used in magnetic resonance imaging. The iodinated contrast
media can cause inappropriate gel barrier formation in blood tubes, which affects the
ST
determination of protein levels in the blood using some methods (26). The
JU
interference of gadolinium contrast agents includes a negative bias in calcium
assessment with the ortho-cresolphthalein colorimetric assays, an occasional positive
bias using some arsenazo reagents, a negative bias in the measurement of
angiotensin-converting enzyme (ACE) and zinc (colorimetric assay), as well as a
positive bias in determinations of creatinine (Jaffe reaction), total iron binding

capacity (TIBC, ferrozine method), magnesium (calmagite reagent) and selenium
(mass spectrometry) (9). Since the elimination half-life of contract media is typically
less than 2 h, blood collection after this period should be recommended in patients
who have received contrast media for diagnostic purposes (9).
Although these classes include the largest numbers of drugs with an impact of
clinical laboratory tests, there are individual drugs across various classes that can
impact different tests.

D
The clinical impact of the known DLTI
TE
The mechanisms by which drugs interfere with laboratory tests are diverse, as
illustrated by the above examples, but the most common mechanisms involve
EP
inhibiting enzymes (either in the patient or an enzyme used for the assay), the
C
induction of fluorescence or coloration in a sample by the drug, an increase in sample

AC
turbidity, chemical cross-reactions, or competitive binding (to an enzyme, antibody or
other indicator). Most of the drugs interfere with laboratory tests by disturbing the
assays for the chemical components in the urine. Urine is the second most common
ST
sample used in the clinical laboratory, after serum and/or plasma. Urine is used
JU
whenever possible because it is convenient and minimally-invasive in terms of sample
collection. In addition, urine is particularly important for the screening of illegal drugs
and many hormone assays.
Although less common than interference with urine-based testing, interference
with blood-based testing (serum or plasma) may be more important in terms of the
clinical impact. This is because urine is usually used to screen for conditions that are
not immediately life-threatening (diabetes, pregnancy, hormone levels, drug use/abuse,
etc.), while blood is more often used for immediate decision-making regarding
potentially life-threatening conditions in the clinical setting (blood cell counts,
hemoglobin level, blood gases, liver enzyme levels, etc.). Thus, while it may be less
common, interference with blood sample-based testing is more concerning (and is
more likely to have a dire clinical impact) than interference with urine-based tests.
The non-emergency nature of the urine testing allows for confirmation testing using
D
another method or for repeated testing under different conditions. This may be part of
TE
the reason why there are more known/documented DLTI for urine than for blood,
although the methods used for urine testing (including, frequently, immunoassays) are
EP
also associated with a higher innate risk of interference.
C
It is difficult to pinpoint which of the DLTI are the most important clinically. No
AC
specific interference has been reported for nine of the 10 most commonly prescribed
drugs (based on a 2010 report, these were hydrocodone, simvastatin, lisinopril,
levothyroxine, amlodipine besylate, omeprazole, azithromycin, metformin and

ST
hydrochlorothiazide (27)), while amoxicillin has been reported to affect glucose

JU
detection by the copper reduction assay. As noted in the section above, several other
relatively common anti-bacterial agents such as cefdinir, rifampin, telavancin
hydrochloride, doxycycline and erythromycin also interfere with laboratory tests. As
shown in Tables 1 and 2, cefdinir interferes with glucose detection via specific assays;
rifampin affects the detection of opiates, folate and vitamin B; telavancin

hydrochloride affects the detection of clotting and urine protein; and both doxycycline
and erythromycin interfere with the fluorescence assays used to detect catecholamines.
Since these drugs are also used relatively often, they have a high potential to cause
clinically-relevant DLTI.
Metronidazole and tinidazole (commonly-used anti-infective agents) both
interfere with various assays that employ reactions that result in free NADH, such as
some liver enzyme (aspartate transaminase (AST) and alanine transaminase (ALT)),
triglyceride, lactate dehydrogenase (LDH) and hexokinase glucose assays, because
D
these agents have absorbance peaks similar to NADH. Isoproterenol and labetalol
TE
(adrenergic agents) both interfere with laboratory tests, but have different activities.
Isoproterenol interferes with the detection of bilirubin, while labetalol affects the
EP
detection of fluorometric assays for catecholamines, normetanephrine and
C
metanephrine, and thin-layer chromatography and radioenzymatic assays for

AC
amphetamines.
Although other methods of detection exist for most of these assays, laboratories
will often not have an alternative method available, and many forms of interference
ST
are not specifically considered by the laboratory staff. In addition, even if the
JU
discrepant finding is due to a DLTI recognized by the laboratory staff, patients may
fail to provide an accurate record of the medications they are taking, making it
impossible to conclude that the abnormal finding is truly due to DLTI. Thus, while the
reported percentages of most types of DLTI that have been examined in previous
studies have been low, the real rate may be much higher due to a lack of confirmation
of the effect and a lack of reporting.
The use of automated systems and electronic medical records to identify potential
DLTI
The large number of prescription drugs and the variety of assays performed,
especially in the hospital setting, can make it difficult for even experienced laboratory
personnel to keep track of the potential DLTI. Moreover, in some cases, patient
samples are assayed by people who are not laboratory professionals or who have
D
limited laboratory knowledge (particularly for waived testing). Therefore, it is
TE
important to understand which drugs interfere with laboratory tests, including their
mode of action and the extent of the impact, so that these personnel (and the clinicians
EP
they report to) fully understand the limitations of the tests (28-31).
C
It was reported almost forty years ago that automatic notification of potential
AC
DLTI could help physicians better interpret test results and choose a better treatment
strategy. Although only 0.1% of treatments were changed based on the notification of
potential DLTI (per changes noted in the medical charts), this would result in
ST
treatment changes in a substantial number of patients given the total number of

JU
patients treated each year in the U.S; additionally, while only 0.1% of the recorded
treatment strategies were changed, the physicians in that study reported more frequent
changes to their selected treatment strategy based on the notification (which may not
have been recorded in the charts at the time) (32). There have also been reports of
other “reminder” systems that were used to warn clinicians and/or laboratory
personnel of potential DLTI based on the patient’s prescriptions (using pharmacy
records) and known DLTI (based on databases existing at the time) (33). Such
reminders can help to ensure that assay results are checked for accuracy in patients at
risk of DLTI prior to being used for clinical decision-making.
However, while the above system was found to be useful, patient records are
frequently incomplete or inaccurate. Moreover, even if the records are accurate, they
may not be transferred between clinics or institutions, or may not be received until
after a course of treatment has begun. This is slowly changing because electronic
D
medical records (EMR) must now be used by all public and private healthcare
TE
providers (in the U.S.) in order for them to receive full payments from Medicaid and
Medicare (beginning in 2015). This mandated use of EMR provides better

EP
opportunities to monitor for potential DLTI, because the use of electronic records
C
permits both the easier transfer of records and the development of additional software
AC
add-ons that can identify discrepant results in the laboratory based on the patients’
prescriptions, health conditions and general clinical picture, even when new (as yet
unidentified) DLTI are present.

ST
Proactive monitoring for potential DLTI is also made possible by the fact that
JU
several related markers are often evaluated at the same time (i.e. lipid parameters,
parent drug and metabolite(s), glucose and HbA1c, etc.). Since the levels of these
various markers are predictably related, a software program can be developed to alert
laboratorians and/or clinicians of potential DLTI if the relationship between known
markers is abnormal. For example, an elevated glucose level (blood or urine),

particularly if noted on more than one occasion, but without a concomitant increase in
the HbA1c, may indicate that part of the testing was affected and raise a flag that there
may have been DLTI.
Shortcomings of the FDA labels
Although the FDA drug labels present in DailyMed provided the most
comprehensive free source of information about DLTI, when we reviewed the drugs
labels we found some shortcomings in that the information provided related to DLTI
D
was insufficient or confusing. Some labels pointed out only that the drug or a specific
TE
dose of the drug did not interfere with a specific assay. This is not enough information
for the physicians and laboratory staff to assess the profile of DLTI for a drug.
EP
Guidance for some specific assays is provided in a few labels. For example, the
information included with naltrexone hydrochloride tablets indicates that “Naltrexone

C
AC
does not interfere with thin-layer, gas-liquid, and high pressure liquid
chromatographic methods which may be used for the separation and detection of
morphine, methadone or quinine in the urine. Naltrexone may or may not interfere
ST
with enzymatic methods for the detection of opioids depending on the specificity of the
JU
test. Please consult the test manufacturer for specific details”. Similarly, the label for
flucytosine capsules indicates that “Measurement of serum creatinine levels should be
determined by the Jaffé reaction, since Ancobon does not interfere with the
determination of creatinine values by this method. Most automated equipment for
measurement of creatinine makes use of the Jaffé reaction.” The information for
gadopentetate dimeglumine injection notes that “MAGNEVIST Injection does not
interfere with serum and plasma calcium measurements determined by colorimetric
assays.” The inclusion of this type of information is useful and should be encouraged.
According to the current FDA guidelines for drug labels (34), the
clearly-documented drug interference with clinical laboratory tests must be presented
in the drugs labels. Although this is helpful and represents a good start to
understanding DLTI, more proactive monitoring for interference is needed. While

some interference may qualify as an adverse event and result in its being reported (e.g.
D
if it leads to significant morbidity or death), most cases of DLTI or suspected DLTI go
TE
unreported. DLTI may not be reported for various reasons, including the fact that it is
often difficult in clinical practice to attribute altered test results to a particular drug,
EP
especially in patients receiving several drugs. In addition, the statements in the drug
labels about reported DLTI are generally vague – they only indicate the potential for
C
AC
interference and sometimes the qualitative result (increase or decrease in the analyte).
The inclusion of specific findings (i.e., the concentration of a drug leading to a mean
Y% change in the target analyte) would be helpful. However, individual laboratory

ST
confirmation would likely still be necessary, since differences in the testing conditions,
JU
the skill level of the staff, and patient populations may lead to differences compared to
those found by the manufacturer or FDA.
Limitations of this review
Although this is a relatively comprehensive review on single-agent

FDA-approved drugs, no multi-ingredient drugs, over-the-counter medications,
supplements, herbal/alternative medicines or “nutraceuticals” (food-derived products
with health benefits) are included. These comprise a large number of chemical entities
that may also affect the results of laboratory tests. However, because there are so
many of these agents, and a paucity of consistent literature on the DLTI of these
agents, their effects are beyond the scope of this review.
Another limitation is that even within the DailyMed database (where

manufacturers are required to provide information about DLTI), only about 12% of
D
the agents actually had specific information available about DLTI (present, absent or
TE
unknown/untested). In addition, some of these labels were not sufficiently detailed.
Thus, there may be other types of interference (perhaps even by commonly-prescribed

EP
drugs) that are currently unknown.
C
Additionally, a general limitation associated with evaluating DLTI is that it is

AC
difficult to gauge the clinical impact of the interference. For example, the outcome of
the test interference may be deleterious but not fatal (e.g. job dismissal due to a false
positive workplace drug test); fatal (e.g. death following a change in warfarin
ST
treatment based on a falsely elevated INR; or harmless (treatment was not changed
JU
because the parameter affected was only one of a set of parameters used to assess a
patient’s status). Moreover, additional testing (using a different assay, confirmation
testing, or testing of a new sample) may lead to correction of a spurious result without
any change to treatment being made based on the preliminary result.

Discussion and perspective
Increasing the awareness of DLTI
DLTI has been gaining increasing interest in the clinical setting and during the
drug development process. As mentioned above, the updated guidelines issued by the
FDA in October 2011 (Warnings and Precautions, Contraindications, and Boxed
Warning Sections of Labeling for Human Prescription Drug and Biological Products
— Content and Format, §201.57(c)(6)(iv)), indicate that information on any known

drug interference with clinical laboratory tests must be briefly noted in the
D
WARNINGS AND PRECAUTIONS section (34). The presence of drug/laboratory
TE
test interference means that the laboratory test results may be inaccurate because the
drug interferes with the assay (e.g., a false positive or negative test result is obtained
EP
that does not accurately reflect the quantity, presence, or absence of the analyzed
C
substance). It should be kept in mind that this does not refer to a situation in which the
AC
test result is accurate, but the findings are outside the normal range because of the
physiological effects caused by the drug or its metabolites.
Although known DLTI must be included in the prescription drug labels according
ST
to FDA regulations, there are currently no FDA guidelines for industry regarding
JU
DLTI studies during drug development. The International Federation of Clinical
Chemistry and Laboratory Medicine (IFCC) issued a proposal for the study of the
effects of drugs on laboratory assays in 1984, and most of the studies published about
DLTI have been designed and carried out according to this proposal or modifications
of the original proposal (35-38). Some DLTI are uncovered during development or
early post-marketing surveillance, and are subsequently reported in the drug label. As
the regulator of drug approval, the FDA should issue official updated guidelines for
DLTI studies in the near future, at least for the most commonly-performed tests.
The role of the instrument and reagent manufacturers
As noted above, the validation protocols for most instruments, at least those used
for high-complexity testing, already take into account potential interference by many
commonly used xenobiotics and substances normally present in the body, and thus
D
help to identify DLTI. Nevertheless, it is not practical for these manufacturers to
TE
identify every possible DLTI. Thus, systems for reporting potential DLTI need to be
developed for new analytical instruments and methods.

EP
The instrument and reagent manufacturers and method developers may represent the
ideal “first-line” for detecting potential DLTI. They have extensive knowledge about
C
AC
the reagents being used, including proprietary information that may not be available
to others but that might help to predict interactions. The current FDA
recommendations regarding testing for DLTI (34) and established ISO/TC212

ST
guidelines
JU
(http://www.iso.org/iso/home/store/catalogue_tc/catalogue_tc_browse.htm?commid=
54916&published=on&includesc=true [last accessed 15 May 2016]) can serve as a
starting point for the testing. The drawback to relying on the instrument and reagent
providers to detect DLTI is that the testing will be performed under ideal conditions,
with optimally maintained instruments and highly skilled staff, that do not always
reflect the actual conditions in the clinical laboratory.
The possibility of implementation of DLTI studies during clinical trials
It may be possible to implement a form of standardized evaluations for potential
DLTI during clinical trials. Clinical trials have strict inclusion and exclusion criteria
that provide relatively well-characterized populations, include close monitoring of
patients (with inpatient monitoring in some cases), and have relatively high rates of
patient compliance with treatment. Although adding additional analyses will further
D
increase the already high costs of clinical trials, standard laboratory panels are
TE
regularly run in patients participating in clinical trials, especially during the initial
safety assessments. All of these factors make it easier to monitor the new drug for
EP
potential DLTI, especially for interactions with common laboratory tests or tests
C
specific to the target population.

AC
DLTI studies during post-marketing surveillance and in daily clinical practice
Another possibility would be to identify DLTI as part of the post-marketing

ST
surveillance. It might be useful for the FDA to start a system for the voluntary
JU
reporting of DLTI, similar to the current systems for reporting drug- and
device-related adverse events. Although some DLTI may fit under the current systems,
it is often unclear whether a spurious test result is truly being caused by the drug or
whether other factors may be involved. Thus, the reporting mechanism would ideally
allow for online submission of suspected DLTI by laboratory staff, physicians or other
medical personnel. Many laboratory technicians have suspicions about specific DLTI,
but do not report them because they are non-life-threatening and have not been
conclusively confirmed to be the sole cause of the spurious finding. There would
likely be an influx of suspected DLTI reports following the introduction of a new drug;
these would help to narrow down the tests potentially impacted by that drug, and the
accumulation of data in such a system would identify drugs that should be assessed
for specific DLTI by the FDA or contract laboratories.

In addition to the FDA, other agencies and regulatory bodies could also develop
D
strategies to address DLTI. For example, the Clinical Laboratory Improvement Act
TE
(regulations enforced by the Centers for Medicare and Medicaid Services) provides
regulatory standards for clinical laboratory testing. Future amendments should

EP
emphasize the importance of DLTI, and training materials should be developed for
C
physicians, laboratory directors, and testing personnel to help them recognize

AC
potential sources of error related to DLTI. This might fit well under the Individual
Quality Control Plan (IQCP) for each lab. Similarly, the Substance Abuse and Mental
Health Services Administration oversees laboratories that perform forensic drug

ST
testing for federally-regulated programs and industries. Although some potential DLTI
JU
for illicit drug testing are known (such as bupropion hydrochloride giving positive
findings for amphetamines in some immunoassays (39)), large-scale prospective
tracking using a reporting system to track unexpected results/cases of unexpected
non-compliance would help to identify potential DLTI that can be confirmed by
experimental studies.
In general, there should be a “call to arms” made by the U.S. (and other)
government agencies to ensure that all physicians and laboratory staff understand the
potential risk of DLTI and make informed decisions regarding patient care based on
this knowledge. With the increasing use of EMR worldwide, software manufacturers
should also strive to help identify potential DLTI based on discrepant results between
the patient’s history or clinical picture or among markers with a known relationship,
and to provide automated notification of the risks of such DLTI.

In the clinical setting, the recording of DLTI and suspected DLTI will require
D
detailed and accurate history-taking, as well as improved transfer of medical records
TE
between institutions. Patient education regarding the importance of a full and accurate
picture of their use of prescription and other drugs (legal and illegal,
EP
physician-prescribed and OTC) is needed, along with physician and staff efforts to
C
ensure that such information has been obtained from all patients.
AC
Of note, patients frequently take more than one prescription drug, or take
prescription drugs along with OTC products, herbal medications, “nutraceuticals”
and/or supplements. The incidence of clinical laboratory test interference by the drugs
ST
in these polypharmacy patients is expected to be higher than the incidence when the
JU
drugs are used individually. A previous study assessed the interference of various
drugs on laboratory tests in 100 outpatients; the percentage of tests affected by
interference was 7% when the patient was taking one drug, 16.7% when the patient
was taking two drugs, 66.7% when the patient was taking three or four drugs, and 100%
when the patient was taking five drugs (40). This is a challenge for drug developers,
instrument manufacturers and clinical laboratory scientists, and collaborative studies
of DLTI for patients receiving multiple drugs or OTC products are needed. The use of
software-based automatic monitoring of test results (including changes in results
compared to those obtained before the drug was taken) will be particularly helpful in
identifying potential DLTI, as well as analytical interference due to OTC medications
and supplements (provided they are reported by the patient).

Existing databases about DLTI
D
A few online databases have been set up to contain information about DLTI. The
TE
largest of these are the DailyMed website used in this review, the AACC Effects on
Clinical Laboratory Tests initially developed in collaboration with Dr. Young

EP
(mentioned earlier; 18); and the First Databank (FDB) MedKnowledge Clinical
C
Modules, Drug-Lab Interference Module (41). Databases in other countries that report
AC
similar information have also been established. These databases can provide useful
information to physicians, laboratory directors and other clinical staff regarding
potential DLTI. While the formats differ, they all allow searches to be performed for
ST
DLTI related to specific drugs. DailyMed is currently the only free database.
JU
To our knowledge, no databases are currently able to be updated by anyone other
than those managing the database. This allowa the accuracy of the data regarding
DLTI to be preserved, but it would be useful for a new database to be developed to
allow the reporting of suspected DLTI by laboratory personnel and clinicians. Several
groups have proposed such databases, including Grönroos et al. (42), but none of
these has become widely used. The rapid changes in technology are likely responsible
for the failure of some of these systems. Given the costs and logistical issues, it will
probably require a federal government or a large organization (such as the World
Health Organization) to fund and manage such a database.
In order to make the database useful, it will need to be free, easily and rapidly
searchable, and ideally allow input from users. A crowd-sourced database in the vein
of Wikipedia might be useful by allowing users who choose to register to add new
content while restricting the ability to change findings that have already been
D
substantiated. Additional users could upload data that supports or refutes a putative
TE
DLTI. This type of reporting would suggest potential DLTI that should be examined
by researchers (or regulatory agencies) that might otherwise not be considered.

EP
C
Future directions and recommendations

AC
The FDA label currently provides the best source of free data about DLTI, but it
has limitations. As noted above, the majority of the drug labels do not currently
contain specific information about DLTI, largely because none exists. Moreover,
ST
much of the information that is included is not sufficiently detailed to inform

JU
clinicians and laboratory staff. This can be remedied by implementing required testing
for DLTI for the most commonly-performed laboratory tests by the instrument and
reagent manufacturers/providers, during clinical trials and as part of early
post-marketing surveillance, as well as by using automated software systems. The
ability to crowd-source data regarding suspected DLTI would also likely accelerate
research on the topic.
Although we have provided a comprehensive review of the single-agent
FDA-approved drugs in the DailyMed database and DLTI in general, we have barely
scratched the surface. The use of multiple prescription drugs, OTC drugs, herbal
products, etc. may also lead to analytical interference, as may prescription drugs
containing more than one active ingredient. There are also many foods that lead to
spurious test results. There is currently little information available about the impact of
most of these substances, although some reports have been published in the literature
D
(43, 44). The publication of standard methods for evaluating DLTI during method
TE
development, in clinical trials and early post-marketing surveillance, the development
of a large-scale database to list and update DLTI, increased assessment and reporting
EP
of DLTI in the clinical setting, and automated notification (perhaps implemented in
C
the EMR) of discrepant laboratory results are all necessary steps that should be taken
AC
as soon as possible to limit the clinical impact of DLTI.
Summary/conclusion
ST
The most significant finding of the present study is that antibacterial and
JU
psychotropic agents and contrast media are the most likely drugs to cause DLTI.
These drugs also account for the majority of the agents used in hospitals and clinics.
Therefore, clinicians should pay special attention when making a diagnosis or
defining a patient’s status based on assay results in patients receiving these classes of
drugs. It also emphasizes the need for a precise and detailed history-taking to ensure
that patients disclose all drugs (prescription and OTC) and supplements (vitamins,
minerals, herbal supplements, nutraceuticals, etc.) that they are using because the
drugs may affect the outcome of laboratory tests.
The information about DLTI should be transmitted and widely disseminated to
clinical laboratories to ensure that all are informed about potential issues. At the same
time, the laboratory staff should be cautious when explaining the assay results for
patients who have taken these drugs. An alternate assay method or reagent that will
not be affected by the specific drug should be used to obtain more accurate results
D
whenever possible. In addition, the inclusion of automated notifications regarding
TE
discrepant laboratory findings (where the results do not agree with the clinical picture
or patient history, or where related markers do not show their usual relationship)
EP
would help to alert laboratory staff and physicians of possible DLTI.
C
In summary, this is the first review offering information regarding the DLTI
AC
described in the labels of FDA-approved drugs. This information should be useful for
the pharmaceutical industry to consider during drug development and for government
regulatory agencies intent on revising industry guidelines. More importantly, it may

ST
serve as a reference for physicians and clinical laboratory staff to obtain better test
JU
results for clinical diagnostics and monitoring.
Acknowledgement
Dr. Haibo Li was supported in part by the International Cooperation and Exchanges
(2012) Program of the Department of Health in Jiangsu Province, China

Declaration of Interest Statement
The authors declare that they have no potential conflicts of interest with regard to this
manuscript.
References
1. The Lewin Group. Laboratory Medicine: A National Status Report. Prepared for: Division of
Laboratory Systems National Center for Preparedness, Detection, and Control of Infectious
Diseases, Centers for Disease Control and Prevention. May 2008. Available at:
https://www.asm.org/images/PSAB/labsys-cdc08.pdf (last accessed 15 May 2016).
2. American Clinical Laboratory Association. Clinical Laboratory Testing: Life Saving
D
Medicine Starts Here. Available at:
http://www.acla.com/wp-content/uploads/2013/12/ACLA_Overview_OneSheet_v07.pdf (last
accessed 15 May 2016).
TE
3. Kandilov AMG, Pope GC, Kautter J, Healy D. The National Market for Medicare Clinical
Laboratory Testing: Implications for Payment Reform Medicare & Medicaid Research
EP
Review A publication of the Centers for Medicare & Medicaid Services, Center for Strategic
Planning 2012;2(2): 1-21. Available at:
https://www.cms.gov/mmrr/Downloads/MMRR2012_002_02_A04.pdf (last accessed 15
May 2016).
C
4. Ismail Y, Ismail AA, Ismail AA. Erroneous laboratory results: what clinicians need to know.
Clin Med 2007;7(4): 357-61.
AC
5. Gulbahar O, Konca Degertekin C, Akturk M, Yalcin MM, Kalan I, Atikeler GF, Altinova
AE, Yetkin I, Arslan M, Toruner F. A case with immunoassay interferences in the
measurement of multiple hormones. J Clin Endocrinol Metab 2015;100(6):2147-53.
6. Kazmierczak SC, Catrou PG. Analytical interference. More than just a laboratory problem.
ST
Am J Clin Pathol 2000;113(1):9-11.

7. COLA Laboratory Accreditation Manual. May 2016:91-92. Available at:
https://clients.cola.org/files/pdf/COLA%20Laboratory%20Accreditation%20Manual.pdf (last
JU
accessed 15 May 2016.

8. Hart MH, de Vrieze H, Wouters D, Wolbink GJ, Killestein J, de Groot ER, Aarden
LA, Rispens T. Differential effect of drug interference in immunogenicity assays. J Immunol
Methods 2011;372(1-2):196-203.
9. Lippi G, Daves M, Mattiuzzi C. Interference of medical contrast media on laboratory testing.
Biochem Med (Zagreb) 2014;24(1):80-88.
10. Tsakiris DA. Direct oral anticoagulants-interference with laboratory tests and mechanism of
action. Semin Hematol 2014;51(2):98-101.
11. Ostrov BE, Amsterdam D. The interference of monoclonal antibodies with laboratory
diagnosis: clinical and diagnostic implications. Immunol Invest 2013;42(8):673-90.
12. Nagase S, Kohguchi K, Tohyama K, Watanabe M, Iwatani Y. Interference by pralidoxime
(PAM) salts in clinical laboratory tests. Clin Chim Acta 2013;416:72-79.
13. de Cordova CM, Nogara MS, de Cordova MM. Interference on the laboratory measurement
of bilirubin: the effect of in vitro interactions. Clin Chim Acta 2009;407(1-2):77-79.
14. Ismail AA. Identifying and reducing potentially wrong immunoassay results even when
plausible and “not-unreasonable”. Adv Clin Chem 2014;66:241-294.
14a. Young DS, Thomas DW, Friedman RB, Pestaner LC. Effects of drugs on clinical laboratory
tests. Clin Chem. 1972 Oct;18(10): 1041-303.
15. Young DS, Pestaner LC, Gibberman V. Effects of drugs on clinical laboratory tests. Clin
Chem 1975;21(5):1D-432D.
16. Forman DT, Young DS. Drug interference in laboratory testing. Ann Clin Lab Sci
1976;6(3):263-271.
17. Young DS. Effects of drugs on clinical laboratory tests. Ann Clin Biochem 1997;34(Pt
6):579-581.
18. AACC Effects on Clinical Laboratory Tests: Drugs, Diseases, Herbs & Natural Products.
John Wiley and Sons, Inc. Available at: http://clinfx.wiley.com/aaccweb/aacc/login. (last
D
19. U.S. Department of Health and Human Services, Food and Drug Administration, Center for
Recommendations. 2012.
TE
Drug Evaluation and Research (CDER). Guidance for Industry. Drug Interaction
Studies-Study Design, Data Analysis, Implications for Dosing, and Labeling
Available at:
EP
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/u
cm292362.pdf. (last accessed 15 May 2016).
20. Logan JE, Haight DE. An evaluation of some commercial test papers and tablets for the
determination of glucose in urine. Can Med Assoc J 1964;91:581-585.
C
21. Bandi ZL, Myers JL, Bee DE, James GP. Evaluation of determination of glucose in urine
with some commercially available dipsticks and tablets. Clin Chem 1982;28(10): 2110-2115.
AC
22. Aspinall PA, Hill AR. Practical problems with the Clinitest. Br Med J 1979;2(6189):552.
23. Webster PS, Oleson FB Jr, Paterson DL, Arkin CF, Mangili A, Craven DE, Adcock DM,
Lindfield KC, Knapp AG, Martone WJ. Interaction of daptomycin with two recombinant
thromboplastin reagents leads to falsely prolonged patient prothrombin time/International
ST
Normalized Ratio results. Blood Coagul Fibrinolysis 2008;19(1):32-8.

24. Amanatullah DF, Lopez MJ, Gosselin RC, Gupta MC. Case report: artificial elevation of
prothrombin time by telavancin. Clin Orthop Relat Res 2013;471(1):332-5.
JU
25. Canfield RE, O'Connor JF, Birken S, Krichevsky A, Wilcox AJ. Development of an assay for
a biomarker of pregnancy and early fetal loss. Environ Health Perspect 1987;74: 57-66.
26. Spiritus T, Zaman Z, Desmet W. Iodinated contrast media interfere with gel barrier formation
in plasma and serum separator tubes. Clin Chem 2003;49(7):1187-9.
27. DeNoon DJ. The 10 Most Prescribed Drugs. WebMD Health News. Published April 20, 2011.
Available at: http://www.webmd.com/news/20110420/the-10-most-prescribed-drugs (last
28. Vasudevan S, Hirsch IB. Interference of intravenous vitamin C with blood glucose testing.
Diabetes Care 2014;37(5): e93-94
29. Khare R, Li J, Lu Z. LabeledIn: Cataloging labeled indications for human drugs. J Biomed
Inform 2014;52:448-456.
30. Reisfield GM, Goldberger BA, Bertholf RL. 'False-positive' and 'false-negative' test results in
clinical urine drug testing. Bioanalysis 2009;1(5):937-952.
31. Scotti da Silva-Colombeli A, Falkenberg M. Analytical interferences of drugs in
the chemical examination of urinary protein. Clin Biochem 2007;40(13-14):1074-1076.
32. Friedman RB, Young DS, Beatty ES. Automated monitoring of drug-test interactions. Clin
Pharm Ther 1978;24:16-21.
33. Kailajärvi M, Takala T, Grönroos P, Tryding N, Viikari J, Irjala K, Forsström J. Reminders of
drug effects on laboratory test results. Clin Chem 2000;46(9):1395-400.
34. U.S. Department of Health and Human Services, Food and Drug Administration, Center for
Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research
(CBER). Guidance for Industry. Warnings and Precautions, Contraindications, and Boxed
Warning Sections of Labeling for Human Prescription Drug and Biological Products-
Content and Format. 2011. Available at:
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm075096.pdf (last accessed 15 May
D
2016).
35. International Federation of Clinical Chemistry (IFCC). Scientific Committee, Clinical
TE
Section. Expert Panel on Drug Effects in Clinical Chemistry (EPDECC). IFCC Document
stage 2, draft 3, 1983-11 with a proposal for an IFCC recommendation. Drug effects in
clinical chemistry. Part 2. Guidelines for evaluation of analytical interference. Clin Chim
EP
Acta 1984;139(2): 223F-230F.
36. CLSI. Interference Testing in Clinical Chemistry; Approved Guideline–Second Edition. CLSI
document EP07-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2005.
37. Sonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and
C
their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38(Pt 4):
376-385.
AC
38. Baer DM, Jones RN, Mullooly JP, Horner W. Protocol for the study of drug interferences in
laboratory tests: cefotaxime interference in 24 clinical tests. Clin Chem
1983;29(10):1736-1740.
39. Reidy L, Walls HC, Steele BW. Crossreactivity of bupriopion metabolite with enzyme-linked
ST
immunosorbent assays designed to detect amphetamine in urine. Ther Drug Monit

2011;33(3):366-368.
40. Kroll MH, Elin RJ. Interference with clinical laboratory analyses. Clin Chem 1994;40(11
JU
Pt 1):1996-2005.
41. FDB MedKnowledge Clinical Modules. Available at:
http://www.fdbhealth.com/fdb-medknowledge-clinical-modules/drug-lab-interference (last
42. Grönroos P, Irjala K, Forsström JJ. Coding drug effects on laboratory tests for health care
information systems. Proc Annu Symp Comput Appl Med Care 1995:449-453.
43. Dasgupta A, Bernard DW. Herbal remedies: effects on clinical laboratory tests. Arch Pathol
Lab Med 2006;130(4):521-528.
44. Lachenmeier DW, Sproll C, Musshoff F. Poppy seed foods and opiate drug testing--where
are we today? Ther Drug Monit 2010;32(1):11-18.
Table 1. FDA-approved single-ingredient drugs that affect urine-based assays
Drug Class or type Type of test(s) or Specific Mechanism of
of drug analyte(s) affected impact on interference (if known)
test(s) or assay affected
Aminosalicylic acid Anti-bacterial Ketones, bilirubin, ND ND
agent urobilinogen or
porphobilinogen
Amoxicillin Anti-bacterial Glucose False Interferes with the copper

agent positive/elevated reduction assay
Ampicillin Anti-bacterial Glucose False Interferes with the copper

Ampicillin Anti-bacterial Glucose False Interferes with the copper

trihydrate agent positive/elevated reduction assay
Bupropion Psychotropic drug Amphetamines False Interferes with screening

hydrobromide positive/elevated immunoassay
D
Bupropion Psychotropic drug Amphetamines False Interferes with screening
hydrochloride positive/elevated immunoassay
Buspirone
hydrochloride
Captopril
Central
system agent
nervous
Cardiovascular
Metanephrine
catecholamines
Acetone
and False
TE
positive/elevated
False
ND
ND
EP
agent positive/elevated
Carbamazepine Analgesic Pregnancy tests* ND ND
Carbidopa Psychotropic drug Ketone bodies False ND

C
positive/elevated
Glucose False-negative Interferes with glucose-oxidase

AC
methods
Cefaclor Anti-bacterial Glucose False Interferes with the copper

Cefazolin Anti-bacterial Glucose False Interferes with the copper

ST
Cefdinir Anti-bacterial Susceptibility results for False ND

monohydrate agent citrobacter, providencia, positive/elevated
JU
and enterobacter spp.*
Ketones False Interferes with tests using

positive/elevated nitroprusside
Glucose False Interferes with the copper

positive/elevated reduction assay
Cefditoren pivoxil Anti-bacterial Glucose False Interferes with the copper

Cefepime Anti-bacterial Glucose False Interferes with the copper

hydrochloride agent positive/elevated reduction assay
Cefixime Anti-bacterial Ketone bodies and False Interferes with the copper
agent glucose positive/elevated reduction assay
Cefotaxime sodium Anti-bacterial Glucose False Interferes with the copper

Cefotetan disodium Anti-bacterial Glucose False Interferes with the copper

Creatinine* False Interferes with the Jaffé

positive/elevated reaction
Cefoxitin sodium Anti-bacterial Creatinine* False Interferes with the Jaffé

agent positive/elevated reaction
17-hydroxycorticosteroids False Interferes with the

positive/elevated Porter-Silber reaction
D
Cefprozil Anti-bacterial Glucose* False Interferes with the copper
Ceftazidime
agent
Anti-bacterial
agent
Glucose FalseTE
positive/elevated
positive/elevated
reduction assay
Interferes with
reduction assay
the copper
EP
Ceftriaxone sodium Anti-bacterial Glucose False ND
Ceftriaxone sodium Anti-bacterial Glucose False Interferes with the copper

C
Glucose* False Interferes with the ferricyanide

AC
negative/decreased assay
Cefuroxime sodium Anti-bacterial Glucose False Interferes with the copper

Glucose* False Interferes with the ferricyanide

ST
Chlorpromazine Psychotropic drug Pregnancy tests* False ND

hydrochloride positive/elevated
JU
Cortisone acetate Anti-inflammatory Bacterial infection False Interferes with the

agent screening test* negative/decreased nitroblue-tetrazolium assay
Dactinomycin Anti-bacterial Antibacterial drug levels* ND ND

agent
Danazol Hormones, Testosterone, ND ND

hormone androstenedione and
substitutes, and dehydroepiandrosterone*
hormone
antagonists
Desvenlafaxine Psychotropic drug Phencyclidine and False Nonspecific antigen

fumarate amphetamine positive/elevated interference
monohydrate
Desvenlafaxine Psychotropic drug Phencyclidine and False Nonspecific antigen

succinate amphetamine positive/elevated interference
Dexamethasone Hormones, Bacterial infection False Interferes with the

sodium phosphate hormone screening test* negative/decreased nitroblue-tetrazolium assay
substitutes, and
hormone
antagonists
Dextroamphetamine Central nervous Steroids ND ND

sulfate system agent
Diatrizoate Contrast medium Proteinuria, specific ND ND

meglumine gravity, osmolality, and
D
bacterial cultures
Diatrizoate Contract medium Proteinuria, specific ND ND

meglumine
Diatrizoate sodium Contrast medium

gravity,
Proteinuria,
osmolality,
bacterial cultures
or
specific ND
TE Various
EP
gravity, osmolality, or
bacterial cultures
Doxycycline Anti-bacterial Catecholamines False Interferes with the

C
agent positive/elevated fluorescence assay
Doxycycline Anti-bacterial Catecholamines False Interferes with the

AC
hyclate agent positive/elevated fluorescence assay
Efavirenz Anti-infective Cannabinoid False Microgenics CEDIADAU

agent positive/elevated Multi-Level THC assay
Erythromycin Anti-bacterial Catecholamines ND Interferes with the fluorometric

ST
agent assay

ethylsuccinate agent assay

JU
lactobionate agent assay

stearate agent assay
Etodolac Analgesic Bilirubin, ketone bodies False Due to the presence of

positive/elevated phenolic metabolites of
etodolac
Ezogabine Central nervous Bilirubin* False ND

system agent positive/elevated
Fludrocortisone Anti-inflammatory Bacterial infection False Interferes with

acetate agent screening test* negative/decreased nitroblue-tetrazolium assay
Gabapentin Analgesic Protein False Interferes with the Ames

positive/elevated n-Multistix sg dipstick assay
Iodixanol Contrast media Protein False Interferes with the Multistix

positive/elevated reagent
Labetalol Adrenergic agent Catecholamines, False Interferes with fluorimetric or

hydrochloride metanephrine, positive/elevated photometric assays
normetanephrine, and
vanillylmandelic acid
Amphetamine False Interferes with thin-layer

positive/elevated chromatographic assays

®
(Toxi-Lab A ) and
radioenzymatic assays
D
®
(Emit-d.a.u .)
Levofloxacin Anti-bacterial Opiate False Interferes with immunoassay
Mefenamic acid
agent
Analgesic Bilirubin False

TE
positive/elevated
positive/elevated
Interferes with dinitrosalicylic
acid assay
EP
Mesna Antidote Ketones False Interferes with nitroprusside
positive/elevated sodium-based assay
Creatinine False Interferes with the thiol

C
phosphokinase* negative/decreased compound (e.g.,

n-acetylcysteine) for CPK
AC
reactivation
Ascorbic acid False Interferes with Tillman's

positive/elevated reagent-based assays
Metaxalone Peripheral nervous Glucose False Interferes with the copper

ST
system agent positive/elevated reduction assay
Methenamine Anti-infective Estriol False Interferes with assays

hippurate agents negative/decreased involving acid hydrolysis
Methocarbamol Central nervous 5-hydroxyindoleacetic ND Interferes with the assays using

JU
system agent acid nitrosonaphthol
Vanillylmandelic acid ND Interferes with assays using the

Gitlow method
Methyldopa Adrenergic agent Uric acid ND Phosphotungstate method

Catecholamines False Fluorescence in urine samples
positive/elevated at the same wavelengths as
catecholamines
Methyldopate Adrenergic agent Uric acid ND Phosphotungstate method

hydrochloride
Catecholamines False Fluorescence in urine samples
positive/elevated at the same wavelengths as
catecholamines
Metyrosine Antineoplastic Catecholamine ND ND

agent
Minocycline Anti-bacterial Catecholamine False Interferes with the

hydrochloride agent positive/elevated fluorescence test
Nafcillin sodium Anti-bacterial Protein False Interferes with the

agent positive/elevated sulfosalicyclic acid test
Nalbuphine Analgesic Opioids ND Interferes with enzymatic

hydrochloride methods
Naproxen Analgesic 17-ketogenic steroids False Interaction between the drug

positive/elevated and/or its metabolites with the
D
m-di-nitrobenzene used in this
assay
Naproxen sodium Analgesic

5-hydroxy
acid (5hiaa)
indoleacetic
17-ketogenic steroids
ND
False
TE ND
Interaction between the drug

EP
positive/elevated and/or its metabolites with the
m-di-nitrobenzene used in this
assay
C
5-hydroxy indoleacetic ND ND
acid (5hiaa)
AC
Niacin Cardiovascular Catecholamines* False Interferes with fluorometric

agent positive/elevated determinations

ST
Nitrofurantoin Anti-infective Glucose False Interferes with the copper

Nizatidine Anti-ulcer agent Bilirubin False Interferes with the Multistix

positive/elevated reagent
JU
Ofloxacin Anti-bacterial Opiates False Interferes with enzymatic

agent positive/elevated methods
Oxaprozin Analgesic Benzodiazepines False Interferes with immunoassay

positive/elevated
Palivizumab Anti-infective Immunological-based rsv ND Interferes with

agent diagnostic tests, viral immunological-based rsv
culture assays* diagnostic tests
Pantoprazole Anti-ulcer agent Tetrahydrocannabinol False ND

sodium (thc) positive/elevated
Penicillin g Anti-bacterial Glucose False Interferes with copper
potassium agent positive/elevated reduction assay
Protein False ND
positive/elevated
Penicillin g sodium Anti-bacterial Glucose False Interferes with the copper

Protein False ND
positive/elevated
Piperacillin sodium Anti-bacterial Glucose False Interferes with the copper

Aspergillus eia test* False Cross-reactions with the

positive/elevated Bio-Rad Laboratories Platelia®
Prazosin Adrenergic agent Vma and metabolite of False ND
D
hydrochloride norepinephrine positive/elevated
Prochlorperazine Psychotropic drug Pku, pregnancy tests* False ND

maleate
Promethazine
hydrochloride
Anti-allergic agent Pregnancy tests* TE
positive/elevated
False-negative or
false-positive
ND
EP
Pyrazinamide Anti-bacterial Ketone bodies False Interferes with the Acetest®
agent positive/elevated and Ketostix® test strips
Quetiapine Psychotropic drug Methadone and tricyclic False Interferes with enzyme
C
fumarate antidepressants positive/elevated immunoassays
Quinine sulfate Anti-infective Protein ND Interferes with the pyrogallol

AC
agent red-molybdate assay
17-ketogenic steroids False Interferes with the Zimmerman

positive/elevated method
Ranitidine Anti-ulcer agent Protein False Interferes with the Multistix®

ST
hydrochloride positive/elevated reagent
Rifampin Anti-bacterial Opiates False Interferes with the KIMS

agent positive/elevated (kinetic interaction of
JU
microparticles in solution)
method
Sertraline Psychotropic drug Benzodiazepines False Interferes with screening

hydrochloride positive/elevated immunoassay
Sotalol Adrenergic agent Metanephrine False Interferes with fluorometric or

hydrochloride positive/elevated photometric methods
Spironolactone Hormones, Digoxin* ND Interferes with

hormone radioimmunoassay
substitutes, and
hormone
antagonists
Succimer Antidote Ketones False Interferes with nitroprusside

positive/elevated reagents such as Ketostix®
Sulfasalazine Analgesic Normetanephrine False Interferes with liquid

positive/elevated chromatography method
Telavancin Anti-bacterial Protein ND Interferes with urine

hydrochloride agent qualitative dipstick protein
assays and quantitative dye
methods (e.g., pyrogallol
red-molybdate)
Thioridazine Psychotropic drug Pregnancy tests* False ND

Tolbutamide Hypoglycemic Albumin False The acidification-after-boiling
D
agent positive/elevated test
Tolmetin sodium Analgesic Protein False Interference of tolmetin
TE
positive/elevated sodium metabolite in urine in
tests that rely on
precipitation as their endpoint
acid
EP
(e.g., sulfosalicylic acid).
Triamterene Diuretic Quinidine* False Triamterene and quinidine

positive/elevated have similar fluorescence
C
spectra
Venlafaxine Psychotropic drug Phencyclidine and False Immunoassay screening tests

AC
hydrochloride amphetamine positive/elevated
Vigabatrin Cns agent Amino acids False ND

positive/elevated
* the assay may be performed on more than one type of matrix (e.g., serum or urine), or the matrix was
ST
not specified in the DailyMed label

ND, not documented/not described (this information was not included in the DailyMed label)
JU
Table 2. FDA-approved single-ingredient drugs that affect blood-based assays
of drug analyte(s) affected impact on interference (if known) or
test(s) assay affected
Alteplase Cardiovascular Coagulation tests and unreliable Degradation of fibrinogen
agent fibrinolytic activity
Aminocaproic Hematological Template bleeding time false Inhibits ADP and collagen-induced
acid agent positive/elevated platelet aggregation, the release of
ATP and serotonin, and the binding
of fibrinogen to platelets
Aminosalicylic Anti-bacterial Albumin ND Dye-binding method

acid agent Ast ND Azoene dye method
Amphotericin b Anti-infective Phosphate false PHOSm assay

Anti-thymocyte Immunological Rabbit antibody-based ND Non-specific reaction

globulin (rabbit) factor immunoassays and
D
cross-match or
panel-reactive antibody
Capromab
pendetide
Indicator/reagent
cytotoxicity assays
Some antibody-based
immunoassays (incl.
false TE
positive/elevated
Presence of human anti-mouse
antibody
EP
PSA and digoxin)
Carbamazepine Analgesic Pregnancy tests* ND ND
Cefadroxil Anti-bacterial Direct Coombs' tests false ND

C
Cefadroxil Anti-bacterial Direct Coombs' tests false ND

AC
hemihydrate agent positive/elevated
Cefazolin Anti-bacterial Direct Coombs' tests false ND

Cefdinir Anti-bacterial Susceptibility results for false ND

ST
monohydrate agent Citrobacter, positive/elevated

Providencia, and
Enterobacter spp.*
Direct Coombs’ test false ND

JU
positive/elevated
Cefditoren Anti-bacterial Direct Coombs' tests false ND

pivoxil agent positive/elevated
Cefixime Anti-bacterial Direct Coombs' tests false ND

Cefotetan Anti-bacterial Creatinine* false Interferes with the Jaffé reaction

disodium agent positive/elevated
Cefoxitin sodium Anti-bacterial Creatinine* false Interferes with the jaffé reaction
Cefpodoxime Anti-bacterial Direct Coombs' tests false ND
proxetil agent positive/elevated
Cefprozil Anti-bacterial Glucose* false Interferes with the copper

Glucose false negative Interferes with the ferricyanide

assay
Ceftibuten Anti-bacterial Direct Coombs' tests false ND

dihydrate agent positive/elevated
Ceftriaxone Anti-bacterial Glucose* false Interferes with the ferricyanide

sodium agent negative/decreased assay
Cefuroxime Anti-bacterial Glucose* false Interferes with the ferricyanide

sodium agent negative/decreased assay
Cephalexin Anti-bacterial Direct Coombs' tests false ND
D
Certolizumab Immunological Activated partial false Interferes with certain coagulation

pegol
Chlorpromazine
factor
Psychotropic drug
thromboplastin
(aptt) assay
Phenylketonuria (PKU)
time
false
TE
positive/elevated assays
ND
EP
hydrochloride test positive/elevated
Pregnancy tests* false ND

positive/elevated
C
Cortisone acetate Anti-inflammatory Bacterial infection false Interferes with the

agent screeing test* negative/decreased nitroblue-tetrazolium assay
AC
Dactinomycin Anti-bacterial Antibacterial drug ND ND

agent levels*
Danazol Hormones, Testosterone, ND ND

hormone androstenedione and
ST
substitutes, and dehydroepiandrosterone*

hormone
antagonists
JU
Daptomycin Anti-bacterial PT and INR False Interacts with recombinant

agent positive/elevated thromboplastin
Dexamethasone Hormones, Bacterial infection False Interferes with the

sodium hormone screeing test* negative/decreased nitroblue-tetrazolium assay
phosphate substitutes, and
hormone
antagonists
Dextran 40 Anticoagulant Glucose False ND

positive/elevated
Bilirubin, protein False Development of turbidity

positive/elevated
Diatrizoate Contrast medium Fibrinogen False Development of turbidity

meglumine concentration; factors V, negative/decreased interfering with the assay
VII, and VIII; platelet
aggregation; serum
calcium; red cell counts;
leukocyte counts
Prothrombin and False ND

thromboplastin times, positive/elevated
urea nitrogen (BUN),
serum creatinine, red

blood cell counts,
leukocyte counts
D
Diatrizoate Contrast medium Fibrinogen False Development of turbidity
sodium concentration; factors V, negative/decreased interfering with the assay
VII, and VIII; platelet
aggregation; serum
calcium; red cell counts;
TE
EP
leukocyte counts
Prothrombin and False Various

thromboplastin times, positive/elevated
urea nitrogen (BUN),
C
serum creatinine, red

AC
blood cell counts,

leukocyte counts
Diflunisal Analgesic Salicylate False ND

positive/elevated
Edetate disodium Anticoagulant Calcium False Interferes with the oxalate method
ST
negative/decreased
Ezogabine Central nervous Bilirubin* False ND

system agent positive/elevated
JU
Fenoprofen Anti-inflammatory Total and free False Chemical cross-reaction

calcium agent triiodothyronine positive/elevated
Fludrocortisone Anti-inflammatory Bacterial infection False Interferes with

acetate agent screeing test* negative/decreased nitroblue-tetrazolium assay
Fosinopril Cardiovascular Digoxin False Interferes with the

sodium agent negative/decreased Digi-Tab®“ RIA Kit
Gadodiamide Contrast media Calcium False Interferes with the colorimetric

Gadoversetamide Contrast media Iron, copper, zinc ND ND

Calcium False decreased Interferes with the
ortho-cresophthalin complexone
(ocp) colorimetric assay
Gadoxetate Contrast media Iron False Due to the presence of caloxetate

disodium negative/decreased trisodium excipients when using
complexometric methods
(ferrocene complexation method)
Iopromide Contrast media Coagulation and False ND

fibrinolysis assay positive/elevated
Iron dextran Hematological Bilirubin False ND

Calcium False Gives a brown color to serum

negative/decreased
D
Isoproterenol Adrenergic agent Bilirubin False ND
sulfate positive/elevated
Isosorbide
mononitrate
Isosulfan blue
Cardiovascular
agent
Coloring agent
Cholesterol
Oxygen saturation
False
TE
negative/decreased
False
Interferes with the Zlatkis-Zak
color reaction
Pulse oximetry
EP
negative/decreased
Methemoglobin False Arterial blood gas analyzers

positive/elevated
C
Kanamycin Anti-bacterial Creatinine False ND

sulfate agent positive/elevated
AC
Mesna Antidote Creatinine False Interferes with the thiol compound

phosphokinase* negative/decreased (e.g., N-acetylcysteine) for CPK
reactivation
Methyldopa Adrenergic agent Creatinine ND Alkaline picrate method

ST
SGOT ND Colorimetric methods
Methyldopate Adrenergic agent Creatinine ND Alkaline picrate method

hydrochloride
SGOT ND Colorimetric methods
JU
Metronidazole Anti-infective SGOP, SGPT, LDH, ND Similarity in the absorbance peaks

agent triglycerides, hexokinase of NADH (340 nm) and
glucose metronidazole (322 nm) at pH 7.
Niacin Cardiovascular Catecholamines* False Interferes with fluorometric

agent positive/elevated determinations
Nitroglycerin Cardiovascular Cholesterol False Interferes with the Zlatkis-Zak

agent negative/decreased color reaction
Ovine digoxin Immunologic Digoxin ND Nonspecific antigen interference

immune fab factor
Palivizumab Anti-infective immunological-based ND Interferes with

agent RSV diagnostic tests, immunological-based RSV
viral culture assays* diagnostic tests
Piperacillin Anti-bacterial Aspergillus EIA test* False Cross-reactions with the Bio-Rad
sodium agent positive/elevated Laboratories Platelia®
Prochlorperazine Psychotropic drug PKU, pregnancy tests* False ND

edisylate positive/elevated
Prochlorperazine Psychotropic drug PKU, pregnancy tests* False ND

maleate positive/elevated
Promethazine Anti-allergic agent Pregnancy tests* False-negative or ND

hydrochloride false-positive
Rifampin Anti-bacterial Folate and vitamin B False Interferes with standard

negative/decreased microbiological assays for folate
and vitamin B
D
Rifapentine Anti-bacterial Folate and vitamin B False Interferes with standard
agent negative/decreased microbiological assays for folate
Spironolactone Hormones,
hormone
Digoxin* ND TE and vitamin B
Interferes with radioimmunoassay

EP
substitutes, and
hormone
antagonists
C
Succimer Antidote Uric acid and CPK False ND

negative/decreased
AC
Telavancin Anti-bacterial PT, INR, aPTT, and ACT False Telavancin binds to the artificial
hydrochloride agent positive/elevated phospholipid surfaces added to
common anticoagulation tests,
thereby
ST
interfering with the ability of the

coagulation complexes to assemble
on the surface of the
phospholipids and promoting
JU
clotting in vitro
Thioridazine Psychotropic drug pregnancy tests* False ND

Tinidazole Anti-infective AST, ALT, LDH, ND Potential interference due to the

agent triglycerides, hexokinase similarity of absorbance peaks of
glucose NADH and tinidazole
Triamterene Diuretic Quinidine* False Triamterene and quinidine have

positive/elevated similar fluorescence spectra
Trifluoperazine Psychotropic drug Phenylketonuria (PKU) False ND

hydrochloride test positive/elevated
Trimethoprim Anti-bacterial Methotrexate ND Competitive binding protein

hydrochloride agent technique (CBPA) when a bacterial
dihydrofolate reductase is used as
the binding protein
Creatinine False Interferes with the Jaffé alkaline

positive/elevated picrate reaction assay
Vigabatrin Cns agent ALT, AST False ND

negative/decreased
*the assay may be performed on more than one type of matrix (e.g., serum or urine), or the matrix was
not specified in the DailyMed label

ND, not described/not documented (this information was not included in the DailyMed label)
D
TE
EP
C
AC
ST
JU

YAO2016

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

YAO2016

Uploaded by

Copyright:

Available Formats

Critical Reviews in Clinical Laboratory Sciences

ISSN: 1040-8363 (Print) 1549-781X (Online) Journal homepage: http://www.tandfonline.com/loi/ilab20

FDA-approved drugs that interfere with laboratory

To link to this article: http://dx.doi.org/10.1080/10408363.2016.1191425

Accepted author version posted online: 18

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

U.S. drug labels

Hospital, Nantong, China

and Drug Administration, Jefferson, AR, USA

Address correspondence to: Haibo Li, Ph.D., Department of Reproductive Medicine,

Nantong Maternity and Child Health Hospital, Nantong, China. Email

Keywords: Drug-related laboratory test interference (DLTI), prescription drugs, FDA

Referees Adel Ismail, Consultant in Clinical Biochemistry and Chemical

Abbreviations and Glossary

AACC, American Association for Clinical Chemistry, a global organization that is

ACE, angiotensin-converting enzyme

AST, aspartate transaminase TE

CBC, complete blood cell count, a common laboratory analysis performed to

determine the numbers erythrocytes, leukocytes and thrombocytes, as well as the

hemoglobin and hematocrit concentrations and mean corpuscular volume

DailyMed, a U.S.-sponsored online database of drug labels that is free to use

DLTI, drug-related laboratory test interference or drug/laboratory test interactions, the

interference of xenobiotic substances with laboratory assays

EMR, electronic medical records

new foods and health-related products

IQCP, Individual Quality Control Plan

but have not been FDA-approved

PT/INR, prothrombin time/international normalized ratio

Drug-related laboratory test interference or drug/laboratory test interactions (DLTI) is

FDA-approved drugs based on a systematic search of DailyMed, a website containing

potential DLTI. The development of a reporting system to address potential DLTI is

The reliance of modern medicine on laboratory testing

The fundamental task of a clinical laboratory is to provide accurate and precise

results for the diagnosis of a disease, determination of its prognosis, indications of

comprehensive metabolic panel[albumin, blood urea nitrogen, calcium, CO2, chloride,

strip/dipstick immunoassays to genetic sequencing and microarrays. As the

substances will increase. The purpose of this review is to provide an updated

interpretation of laboratory tests. We also discuss the existing reporting of these

drug-related laboratory test interference (DLTI).

The implications of drug-related laboratory test interference

Although new instruments and methods are constantly being developed to

treatment, or an incorrect evaluation of a patient’s drug use or compliance with the

interference to lead to a lost opportunity for treatment or to treatment with an

inappropriate therapy that would potentially lead to morbidity or death.

immunoassays ranged from 0.4-4.0% (4). Although a accuracy rate of 99.5% is

will add to the cost and complexity of these tests.

the instrument and reagent manufacturers, government regulatory bodies, and

development of devices/instruments and new testing methods by manufacturers that

in the laboratory. There may be a different spectrum of interference due to differences

in the instrument performance in the laboratory (e.g. effects of temperature and

humidity), differences in the patient population (e.g. different ethnicity, underlying

the instrument/reagent provider and by the end user.

laboratories developing methods to identify all potential sources of cross-reactivity or

drug-related interference during method validation. In addition, while validation is

made to continue monitoring for interference and to record cases of suspected

initial method development and validation.

altering the pharmacology/ADME (absorption, distribution, metabolism and excretion)

interference with laboratory tests.

American Association for Clinical Chemistry (AACC) of a large online database in

potential DLTI are needed.

Aims of this review

these keywords included “analy”, “artifact”, “assay”, “clinic”, “determine”,