Download False-positive DOA testing results due to prescription

CLINICAL ISSUES
False-positive DOA testing results
due to prescription medications
By Amitava Dasgupta, PhD
M
any over-the-counter, or OTC, medicines containing
pseudoephedrine, ephedrine, or other sympathomimetic
amines interfere with screening tests for amphetamines
but do not cause positive test results in the gas chromatography/
mass spectrometric, or GC/MS, confirmation, thus pose no serious challenge in drugs-of-abuse (DOA) testing. In contrast, several prescription medicines containing opioid, amphetamines,
or other ingredients can cause positive confirmed results in
DOA testing. Use of Marinol to control severe pain produces a
positive confirmatory test for marijuana metabolite (11-nor-9carboxy-Δ9-tetrahydrocannabinol; THC-COOH) in urine.
Although the presence of benzodiazepines in urine is not
always tested in federal workplace drug testing (five Substance
Abuse and Mental Health Services Administration, or SAMHSA,
drugs are amphetamines, cocaine as benzoylecgonine, opiates,
marijuana as THC-COOH, and phencyclidine), private employers may test for benzodiazepines in a drugs-of-abuse panel. It is
important for an individual undergoing workplace drug testing
to report the use of such prescription medication and name of the
prescribing physician so the Medical Review Officer can contact
the physician and verify medical use of such controlled substances. Otherwise, employment may be denied or other adverse
action may be taken by the employer against that individual.
Interference with amphetamine/methamphetamine tests
Some prescription medications contain amphetamine or methamphetamine, while the active ingredient of some prescription
medication may be metabolized to amphetamine or methamphetamine, causing positive amphetamine/methamphetamine
test results (see Table 1).1 For example, Adderall contains a
mixed amphetamine salt widely prescribed as a psychostimulant
medication for attention deficit hyperactive disorder, or ADHD,
and use of such medication would cause a positive amphetamine
test. In January 2002, the U.S. Food and Drug Administration
approved Paremyd eye drops which contain hydroxyamphetamine and tropicamide. Although amphetamine is metabolized
to hydroxyamphetamine, hydroxyamphetamine is not metabolized to amphetamine. Therefore, use of such products should
not cause a positive amphetamine test result.
Opiate test results
Several prescription medications for pain management contain
morphine, codeine, hydrocodone, oxycodone, or related opioid.
Oxycodone has variable cross-reactivity with different opiatescreening assays, and there is also a specific immunoassay
which recognizes the presence of oxycodone in urine — but
taking codeine or morphine containing analgesic medication
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produces positive opiate test results in drugs-of-abuse testing.
Ingestion of fentanyl-containing drugs (which are also opioid)
or use of the Duragesic fentanyl patch should not cause a positive opiate test because fentanyl has very poor cross-reactivity
against antibodies used in opiate-screening assays, which recognize morphine and related substances only.
Active ingredient
Amphetamine
Methamphetamine
Brand names
Adderall, Biphetamine, Dexedrine, Dextrostat,
Desoxyn
Active ingredient metabolized to amphetamine
Amphetaminil
Clobenzorex
Ethyl amphetamine
Fenoproporex
Mefenorex
Prenylamine
Aponeuron
Aselin, Asenlix, Dinintel, Finedal, Rexigen
Apetinil
Falagan, Lipolin
Rondimen, Pondinil, Anexate
Segontin, Segentine
Active ingredient metabolized to methamphetamine
Benzphetamine
Furfenorex
Selegiline
Didrex
Withdrawn due to abuse potential.
Carbex, Deprenyl, Eldepryl
Table 1. Drugs that contain amphetamine or methamphetamine, or metabolize to
amphetamine or methamphetamine.
Marinol converts to marijuana metabolite
Although marijuana is a Schedule I drug, a synthetic tetrahydrocannabinol (Marinol) is used for treating nausea and
vomiting in cancer patients undergoing chemotherapy and
also as an appetite stimulant to patients with AIDS. Because Marinol is also converted into marijuana metabolite
(THC-COOH), it causes positive marijuana test; however,
Δ9-tetrahydrocannabivarin (THCV), which is a natural constituent of cannabis product, is absent in Marinol. THCV
is metabolized by human liver into THCV-COOH, and the
presence of this metabolite, in addition to THC-COOH in
urine, indicates abuse of marijuana rather than prescription
use of Marinol.2
Benzodiazepines-containing drugs
Although benzodiazepine is not part of the five federally mandated drugs for workplace testing, many private companies
test for benzodiazepines as a part of their employment drugtesting program. Benzodiazepines is one class of the most
frequently prescribed drugs in the United States, and these are
used as tranquilizers, muscle relaxants, and anticonvulsants as
well as to treat symptoms of anxiety. More than 50 different
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CLINICAL ISSUES
types of benzodiazepines exist, but not
all 50 drugs are available in the United
States. The most commonly prescribed
benzodiazepines in the United States
are diazepam, temazepam, alprazolam,
lorazepam, and clonazepam. Other
examples of derivatives in this class
include areestazolam, halazepam, and
quazepam.
Usually, immunoassay screening for
benzodiazepines recognizes the presence
of common drugs and metabolites after
medical use or abuse. ElSohly, et al,
analyzed benzodiazepines in 156 urine
specimens from alleged victims of drugfacilitated sexual assault and observed
that oxazepam was confirmed in 50% of
the specimens followed by nor-diazepam
(48%), temazepam (43%), and diazepam
(40%), while the presence of alprazolam
was confirmed in 21.8% specimens and
lorazepam in 15.4% specimens.3
Propoxyphene medications
Propoxyphene, a milder narcotic analgesic than benzodiazepines, is used in treat-
ing mild to moderate pain, and is sold
under trade names of Darvocet, Darvon,
Propacet, and Wygesic. Because this
drug is also abused, it, too, is sometimes
tested in private employers’ workplace
drug-testing programs. Prescription use
of propoxyphene may cause a positive
test result because the cut-off concentration for propoxyphene in urine (300 ng/
mL) can be reached after medical use
of this drug.
Medical exposure to cocaine
Cocaine is used infrequently as a local
anesthetic in ear, nose, and throat surgery, and also is administered topically
during ophthalmitic procedures. Positive drug-testing results for cocaine (as
benzoylecgonine, the major metabolite)
may be encountered in subjects who
have undergone such procedures. A
patient may be positive up to 72 hours
after an otolaryngologic procedure
where cocaine is used as an anesthetic.
Cocaine metabolite can also be detected
in the urine specimen of the physician
who is performing the procedure.4
Jacobson, et al, studied the effect
of use of ophthalmic solution containing cocaine on urine excretion of
benzoylecgonine in patients. Out of
50 subjects studied, 47 subjects (94%)
demonstrated a positive screening result for cocaine (as benzoylecgonine)
four to six hours after receiving eye
drops. In addition, 35 subjects (70%)
showed positive results 24 hours after
receiving eye drops containing cocaine.
The authors conclude that ophthalmic
administration of cocaine may cause
positive test results up to two days after
procedure.5
Novocain, although synthetically
derived from cocaine, has a distinct
structural difference from cocaine and
the metabolite of cocaine (benzoylecgonine). Therefore, use of Novocain during dental procedures or use of other
anesthetic agents, including benzocaine,
tetracaine, and lidocaine, should not
cause false-positive cocaine test results
in urine DOA testing.
Conclusion
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Because these drugs are often abused,
medical review officers and healthcare
providers must be aware of true positive
results due to use of such drugs as lawful
medications. Verification of medical use of
such drugs is important in order to determine whether an individual tests positive
for DOA due to the medical use of such a
drug with a valid prescription.
Amitava Dasgupta, PhD, is professor of Pathology and
Laboratory Medicine at the University of Texas Health
Sciences Center-Houston.
References
1.Musshoff F. Illegal or legitimate use? Precursor
compounds to amphetamine and methamphetamine.
Drug Metab Rev. 2000;32:15-44.
2.ElSohly MA, deWit H, Wachtel SR, Feng S, et al. Delta
9-tetrahydrocannabivarin as a marker for ingestion of
marijuana versus Marinol: results of a clinical study.
J Anal Toxicol. 2001;25:565-571.
3.ElSohly MA, Gul W, Murphy TP, Avula B. LC-(TOF) MS
analysis of benzodiazepines in urine from alleged
victims of drug facilitated sexual assault. J Anal
Toxicol. 2007;31:505-514.
4.Bruns AD, Zeiske LA, Jacobs AJ. Analysis of the
cocaine metabolite in the urine of patients and physicians during clinical use. Otolaryngol Head Neck
Surg. 1994;111:722-726.
5.Jacobson DM, Berg R, Grinstead GF, Kruse JR. Duration of positive urine for cocaine metabolite after ophthalmic administration: implications for testing patients
with suspected Horner syndrome using ophthalmic
cocaine. Am J Ophthalmol. 2001;131:742-747.
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