False-positives in urine drug screening caused by medications

Testing urine for the presence of drugs has a variety of uses including assessing poisoning or overdose, pre-employment testing, substance abuse treatment monitoring, or other medicolegal purposes.  There are a number of common medications that can cause false-positive screening of these tests which can lead to a variety of ramifications.

Initial tests are usually performed with an immunoassay.  These can generally be done quickly (an hour or two) and inexpensively and vary in their sensitivity.  They may miss particular substances (for opioids in particular – synthetic or semisynthetic opioids such as hydrocodone, oxycodone, fentanyl, or methadone may not test positive on the initial immunoassay) so if you’re suspicious/concerned about a certain agent, let the lab know so the correct test is performed.  Following the immunoassay, positive results can be confirmed with a more specific technique such as gas chromatography or mass spectrometry but these tests are more costly and time consuming so results may not be available for hours to days. 

Here is a table of medications that can cause false-positives on the urine immunoassay and some comments about the caveats of each category.

Drug	Detection time	May cause false positive	Comments
Amphetamines	2 days; up to 2 weeks with prolonged use	Ephedrine, pseudoephedrine, ephedra, phenylephrine, selegiline, chlorpromazine, promethazine, trazodone, bupropion, desipramine, amantadine, ranitidine, brompheniramine, labetalol, phentermine, methylphenidate	Many of these are available OTC and in OTC combination products which patients frequently don’t mention in their history unless specifically asked.  Even something like Vicks Inhaler falls in this category.  Mefenamic acid (an NSAID) may cause a false-negative.
Barbiturates	1-7 days (short acting); 1-3 weeks (intermediate acting)	Phenobarbital, NSAIDs
Benzodiazepines	Up to 2 weeks; up to 6 weeks with chronic use of long acting	Sertraline	Lorazepam or clonazepam may not be detected on immunoassay.  Flunitrazepam may also not be detected (that’s also the ‘date rape drug’ or ‘roofies’.
Cocaine	12-72 hours; 1-3 weeks with prolonged use		Other anesthetics ending in –caine are not likely to cause a false positive because the test is actually for the cocaine metabolite which these do not produce.  Topical cocaine (used legitimately for anesthesia) can cause a positive test.
Lysergic acid (LSD)	24-48 hours
Marijuana	7-10 days; ~1 month with prolonged use	Ibuprofen, naproxen, efavirenz, dronabinol	Again, these NSAIDs are OTC and may not be garnered immediately in a history.  Passive inhalation is unlikely to exceed the concentration threshold to cause a positive result.
Methadone	3-14 days	Doxylamine (OTC sleep aid like diphenhydramine)
Opioids	2-3 days; 1 weeks with prolonged use or extended release	Rifampin, fluoroquinolones, poppy seeds (these aren’t really false-positives – they’re actually true-positives b/c they contain morphine but they’re not an indicator of drug abuse), quinine (also in tonic water)	Fentanyl, meperidine, methadone, pentazocine, tramadol have minimal cross reactivity and may not be detected.  Mefenamic acid (an NSAID) may cause a false-negative.
Phencyclidine (PCP)	2-10 days; ~1 month with prolonged use	Ketamine, dextromethorphan, diphenhydramine, sertraline, venlafaxine, ibuprofen, imipramine, thioridazine, tramadol

There are a number of drugs that may be relevant that are not detected by routine drug screening.  Some examples are:

• Anabolic steroids, dietary supplements, hydrocarbon solvents (which people may inhale recreationally), or gamma-hydroxybutyrate (GHB – used recreationally or for ‘date rape’)

Take home points:

• Emergency care may or may not be affected by the results of a urine toxicology screen but it can be helpful to verify substances claimed to be taken or identify other toxins that were co-ingested.
• Numerous medications can cause false-positives on the initially available immunoassay but the sample can be further analyzed by mass spectrometry or gas chromatography to determine the true substance.
• Not all benzodiazepines or opioids will test positive on an initial immunoassay.  Contact the lab to find out is the immunoassay is sensitive to the agent(s) in question.
• Contact the lab in advance if you are suspicious or concerned about a specific agent, since the best test to perform may vary.
• Be sure to ask about OTC products including topicals and inhalers since patients often overlook these as being medications.

References:

1.  Chyka PA.  Substance abuse and toxicological tests.  In: Lee M.  Basic skills in interpreting laboratory data.  Bethesda, MD: ASHP; 2009:39-72.

2.  L Detail-Document, Urine Drug Testing. Pharmacist’s Letter/Prescriber’s Letter.  March 2014.

3.  Mandatory guidelines for federal workplace drug testing programs.  Department of Health and Human Services.  Substance abuse and mental health services administration.  Federal register / Vol. 73, No. 228/ November 25, 2008.

photo by Kevin Lau