Alyson Schwebach, PharmD Candidate 2016Student PharmacistSouth Dakota State UniversityCollege that PharmacyBrookings, southern Dakota

Jennifer Ball, PharmDAssistant Professor of Pharmacy PracticeSouth Dakota State UniversityCollege of PharmacyBrookings, southern DakotaClinical Pharmacist, center for household MedicineAdjunct Assistant Professor of family MedicineUniversity of southern Dakota school of MedicineSioux Falls, south Dakota

US Pharm. 2016;41(8):26-30.

ABSTRACT: Urine drug screening is a common means to test for compliance with medications having actually high abuse potential. False-negatives and false-positives indigenous immunoassays have the right to lead come adverse results for patients and also providers. Through identifying medications that contribute to false-negatives and false-positives, pharmacologists decrease misinterpretations from urine medicine screens. Unexpected results from urine immunoassays should have actually a confirmatory gas chromatography–mass spectrometry or a high-performance liquid chromatography test performed. Pharmacists can provide guidance in selecting suitable drug therapies that are much less likely to cause false readings, for this reason decreasing the require for added testing.

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Urine drug display screen (UDS) experimentation can rise workplace safety, detect drug abuse, screen patients’ compliance v prescription medications, and assess suspected drug ingestions.1 Thus, these tests are typically used in clinical exercise to support decision-making ~ above the usage of high-risk medications. The most typically used form of UDS is the immunoassay as result of its low cost, rapidity the results, and simplicity that use. Immunoassays recognize substances above a collection threshold utilizing antibodies.1,2 if a advantageous tool, immunoassays have poor specificity the may cause false-positive results.1-3 unanticipated results need to be evidenced with a second test, such as gas chromatography–mass spectrometry (GC-MS) or high-performance liquid color layer analyzer (HPLC), the is more accurate; however, this tests space costly and also require extra time come perform.1-3 Therefore, patient care decisions are often made based upon presumed confident or negative immunoassay test results.

Interpreting check Results

Misinterpretation that UDS outcomes may have actually adverse consequences for patients, consisting of unwarranted ns of a job, potential criminal charges, ns of qualification indigenous sporting occasions or rehabilitation programs, potentially improper medical treatment, or ns of to trust from healthcare professionals.2,3 Patients that are forced to receive random or recurrent UDS trial and error as component of rehabilitation programs; as a stipulation of employment; for wellness monitoring, such as for pain monitoring or medication compliance; or for other reasons room at an especially high threat of an unfavorable consequences from misinterpreted UDS results.1,4 to decrease the likelihood that misinterpretation, pharmacists can assist by identifying drugs at high hazard for leading to false-negatives and false-positives and choosing medications much less likely to cause these inaccuracies.

False-Negatives: To aid in interpreting UDS results, pharmacists should acquire a thorough perform of every the patient’s prescription, OTC, and herbal drugs prior to testing, and also discuss adherence to medications. Once a an adverse screening an outcome is obtained, pharmacists should closely consider the potential because that a false-negative result, especially for patient receiving UDS trial and error to assess compliance through a medication regimen or for those exhibiting actions or risk components suggestive of medicine abuse or medicine dependency.1

False-negatives can happen when the urine drug concentration is below the threshold level set by the activities performing the test.1,2 Dilute urine, the expression of time in between ingestion the the drug and time of testing, and also the quantity of the medicine ingested may impact the incident of false-negatives.1-2 if chronic marijuana usage will show in the urine because that weeks after heavy use, various other medications and also illicit medicine will just be current for 1 to 4 days, as shown in TABLE 1.1-4


Patients may purposefully attempt to hide positive screening results by adding contaminants to their urine that mask the visibility of a drug, such together vinegar, soap, bleach, drain cleaner, eye drops, table salt, or ammonia.5 Additionally, commercial commodities with the active ingredients peroxide (peroxidase), glutaraldehyde, salt or potassium nitrite, and pyridinium chlorochromate might be used.5 transforms in pee appearance, color, specific gravity, or pH may suggest the visibility of a contaminant and should it is in checked. Patient may additionally drink an excessive amount of water (2-4 qt) or usage diuretics come purposefully dilute your urine and also the urine drug concentration to decrease the opportunity of detection.5,6

Furthermore, false-negatives may additionally occur due to the fact that the UDS is just unable to detect the agent. For example, UDS tests for benzodiazepines commonly an outcome in false-negatives for agents the have poor cross-reactivity v the assay.7 most assays for benzodiazepines detect their existence in the to pee by testing for nordiazepam and oxazepam, the key metabolites of many benzodiazepines.2 Agents the follow a various metabolic pathway, such as triazolam, alprazolam, clonazepam, and also lorazepam, have poor cross-reactivity with the assay as result of the absence of this metabolites and also thus typically produce false-negative results.2,7 Therefore, come decrease the need for confirmatory testing, diazepam, oxazepam, and also temazepam might be preferred.

Similarly, opiates can be at risk for false-negatives. Many immunoassay exam look for morphine, norcodeine, and codeine; for this reason morphine, heroin, and codeine can quickly be detected. Hydrocodone and hydromorphone are metabolites that codeine and are rarely confident on immunoassay tests. Oxycodone, buprenorphine, and tramadol monitor a separate metabolic pathway, and fentanyl might not be detected because it lacks metabolites.1,4 To minimization the require for confirmatory testing, consider using morphine or codeine in high-risk patients.

For patients gift treated because that attention-deficit/hyperactivity disorder (ADHD), UDS testing may also be recommended. Immunoassays test because that amphetamines; thus, amphetamine, dextroamphetamine, and lisdexamfetamine products should return confident results because that compliance trial and error if take away in the critical 2 to 3 days. Illicit methamphetamine will likewise show hopeful within the amphetamine immunoassay test. However, methylphenidate products do no cross-react through amphetamines and also will commonly produce an unfavorable results,8 although a false-positive result with methylphenidate has been watched in one pediatric case report.1-2,8 If methylphenidate assets are used, a GC-MS test should be consistently administered.

False-Positives: In enhancement to false-negatives, pharmacists need to take into consideration the potential for false-positive UDS results and be aware of drugs that may reason false-positives. TABLE 2 summarizes countless medications that have actually been reported to cause false-positive outcomes with usual substances of abuse or tricyclic antidepressants (TCAs).1-4 False-positives can take place when a medication has actually a cross-reactivity through the immunoassay, often because of a similarity in the structure of the parental medication or among its metabolites to the experiment drug.2 The incident of false-positives is mostly influenced by the kind of immunoassay used and by the certain agent gift tested.2


When picking therapeutic agents because that high-risk patients, pharmacists should consider minimizing the usage of drugs known to reason false-positive results, if possible. The an option of an ideal therapeutic agent because that a patient counts on numerous factors, such as the effectiveness and also adverse-effect profile of the drug; therefore, minimizing the usage of medications displayed to cause false-positives should be weighed against clinical referee in product selection. However, for patients undergoing regular UDS testing, selecting an agent the very least likely to cause false-positives would be crucial consideration to aid minimize adverse results to patient from potentially misinterpreted results.


Many that the drugs reported to reason false-positive UDS results encompass a variety of antidepressants, which deserve to be supplied for miscellaneous indications. Of the selective serotonin reuptake inhibitors (SSRIs), sertraline has actually been report to reason false-positive results for benzodiazepines and lysergic acid diethylamide (LSD),1-4,9 and fluoxetine has been report to reason false-positive results for LSD and amphetamines.1,3,9 Bupropion and also trazodone have likewise been report to cause false-positive LSD and amphetamine results, v the communication to the amphetamine assay credited to cross-reactivity through the agents’ metabolites.1-4,9 Additionally, numerous reports have uncovered venlafaxine to cause false-positive phencyclidine (PCP) results.2-4 while both venlafaxine and its active metabolite, O-desmethylvenlafaxine, room structurally dissimilar to PCP and also have extremely low cross-reactivity (0.0125% and 0.025%, respectively), the concentrations of the two together have been hypothesized to cause the false-positive results.2,4

Furthermore, almost all TCAs can cause false-positive UDS results. Amitriptyline, desipramine, doxepin, and also imipramine have been reported to reason false-positive outcomes for LSD,3 and desipramine and doxepin have in addition been reported to reason false-positive outcomes for amphetamines.1,2 While rarely used, the monoamine oxidase inhibitor (MAOI) selegiline may likewise cause false-positive amphetamine results due to its l-amphetamine and also l-methamphetamine metabolites.2,4

Minimizing the usage of these agents in high-risk patient when feasible may to decrease the hazard of false-positive results. For patients inquiry an SSRI, pharmacologists should think about using paroxetine, citalopram, or escitalopram and also minimizing the use of fluoxetine and sertraline as soon as appropriate. As soon as using an antidepressant come treat neuropathic pain, minimizing the usage of venlafaxine and TCAs and instead utilizing duloxetine must be considered. Gabapentin and pregabalin have a minimal risk of bring about false-positives and also are other choices that could be used. Trazodone is one antidepressant frequently used as a sleep aid. Minimizing the use and instead using mirtazapine or sedative-hypnotics when suitable would be an additional consideration.1-4


In addition to antidepressants, countless antipsychotic agents have likewise been reported to cause false-positive results. Antipsychotics may be used to treat a variety of psychiatric disorders, with the second-generation antipsychotics (SGAs) used much more frequently due to their more favorable side-effect profile compared to the first-generation antipsychotics (FGAs). The the SGAs, risperidone has actually been report to reason false-positive LSD results;3,9 quetiapine, false-positive methadone and TCA results, which are attributed to quetiapine’s resemblance in framework to methadone and also TCAs.2-4 Two instance reports of inadvertently aripiprazole ingestion in pediatric patients resulted in false-positive amphetamine results.10 whether false-positives with aripiprazole may also occur in adult is uncertain.10 The FGAs chlorpromazine, prochlorperazine, haloperidol, and thioridazine might all cause false-positive LSD results.3 Thioridazine may in addition cause false-positive amphetamine, methadone, and PCP results, and also chlorpromazine reason false-positive amphetamine (due to similarities in structure) and also methadone results.1-4

When selecting an antipsychotic agent for high-risk patients, consideration should be given to using lurasidone, olanzapine, or ziprasidone once appropriate. Aripiprazole may likewise be a reasonable alternative in adults, together no reports have found false-positive outcomes in this population. However, pharmacists should very closely consider the opportunity of a positive an outcome being false need to one happen with a patience on aripiprazole. Numerous of the FGAs reason false-positive UDS results and have a less favorable side-effect profile compared to the SGAs; thus, minimizing use of these agents when feasible would it is in suggested.1-4

Other central Nervous device (CNS) Medications

Other CNS agents that have been report to cause false-positive UDS results incorporate buspirone, carbamazepine, and lamotrigine (TABLE 2).1-4 Minimizing use of this agents when possible can also assist reduce the hazard of false-positive results.


In enhancement to the antiemetics promethazine and also doxylamine, metoclopramide and also prochlorperazine have had documented false-positive LSD results.3 take into consideration minimizing the usage of this agents and selecting 5-HT3 receptor antagonists such together ondansetron to decrease false readings in high-risk populations.3


Most antibiotics have actually not been shown to cause false-positives with UDS immunoassays; however, quinolones and also rifampin have actually been recorded in tiny studies.4 every quinolones have the potential to reason a false-positive opiate screening result, through levofloxacin and also ofloxacin having actually the highest risk. Ciprofloxacin, moxifloxacin, and norfloxacin showed cross-reactivity to opiates due to the fact that of similar molecular structures, but at lower levels than most immunoassay thresholds. Thus, these agents may be much less likely to cause false-positives.4,11-12 Ofloxacin has likewise been reported to reason a false-positive amphetamine result.3 In enhancement to quinolones, rifampin has been displayed to cause false-positives for opioids, and elimination calculations estimate a possible false-positive result for an ext than 18 hours after a solitary oral sheep of rifampin 600 mg.13


Determining what OTC products patients room taking is very important when using UDS testing, as some OTCs may cause false-positive results. Antihistamines, analgesics, cough suppressants, and heartburn medications have been shown to reason false-positives in studies and case reports.1-4

False-positive methadone levels have actually been documented with diphenhydramine 100 to 200 mg2-4,14 and doxylamine intoxication.4,15 Additionally, doxylamine intoxication has created false-positive opiate14 and also PCP2 levels, and also brompheniramine use may cause false-positive amphetamine4 and also LSD3,9 levels. Think about using second-generation antihistamines, as they have not been reported to reason false-positive UDS results.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have additionally been displayed to communicate with UDS immunoassays. Both ibuprofen and also naproxen have been recorded to cause false-positive barbiturate4 and also cannabinoid1-4 levels. In addition, ibufrofen can cause a false-positive PCP level.1-2,4 think about minimizing the usage of NSAIDs in high-risk patients and recommending paracetamol instead.

The sneeze suppressant dextromethorphan may reason false-positive PCP1,2,4 and also opioid levels because of its metabolite’s similarity come the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and also pseudoephedrine have presented false-positive amphetamine level due to similar structures.1,2 To protect against misinterpretations, take into consideration limiting these medications in high-risk populations.

Lastly, heartburn medications have actually been documented to communicate with UDS test to reason false-positives. Ranitidine has actually been presented to cause false-positive results for amphetamines at sheep of 150 to 300 mg daily.16 on the other hand, pantoprazole has actually caused false cannabinoid results.1,2 consider using various other histamine blockers (e.g., famotidine) or proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole) not shown to reason false-positives.


Herbal assets may also interfere through UDS immunoassays. As morphine and also codeine are acquired from opium poppy seeds, the input of reasonably small quantities of poppy seeds may result in false-positives for opiates, including the consumption of poppy-seed cookie (having ~1 tsp of poppy-seed filling) or poppy-seed bagels.2 Additionally, the ingestion of foods items containing hemp, such as hemp-seed oil, have actually resulted in hopeful marijuana UDS results,2 and ephedra-containing commodities may reason false-positive methamphetamine results.17

Other organic supplements may be much less likely to cause false-positive test results. A study of gingko biloba, witnessed palmetto, St. John’s wort, ginseng, garlic, environment-friendly tea, valerian, and cranberry did not cause any false-positive reactions.18 Similarly, natural teas and drinks did not cause any false-positives.19 closely assessing patient use of these products can assist minimize misinterpretation of UDS results.


By recognizing usual causes and medication concerns for false-negatives and false-positives in UDS testing, pharmacists deserve to improve treatment and provide insight into alternative medications for patients. In every cases, clinical judgment have to be supplied in picking an ideal therapeutic agent. Unexpected outcomes from a UDS immunoassay must be checked with a confirmatory GC-MS or HPLC test. By reducing medication-related causes of false-positives and also false-negatives, pharmacists can potentially diminish the need for added testing and also the negative consequences of misinterpreted to pee immunoassay testing, hence optimizing patient care.

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1. Standridge JB, Adams SM, Zotos AP. Urine drug screening: a valuable office procedure. Am Fam Physician. 2010;81(5):635-640.2. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical overview for clinicians. Mayo Clin Proc. 2008;83(1):66-76.3. Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387-396.4. Brahm NC, Yeager LL, Fox MD, et al. Generally prescribed medications and potential false-positive urine medicine screens. Am J health Syst Pharm. 2010;67(16):1344-1350.5. Jaffee WB, Trucco E, levy S, Weiss RD. Is this urine really negative? A systematic evaluation of tampering methods in urine drug screening and testing. J Subst Abuse Treat. 2007;33(1):33-42.6. Cone EJ, Lange R, Darwin WD. In vivo adul-teration: excess fluid ingestion reasons false-negative marijuana and also cocaine urine test results. J Anal Toxicol. 1998;22(6):460-473.7. Johnson-Davis KL, Sadler AJ, Genzen JR. A retrospective analysis of urine drugs of abuse immunoassay true optimistic rates at a nationwide reference library. J Anal Toxicol. 2016;40(2):97-107.8. Breindahl T, Hindersson P. Methylphenidate is identified from amphetamine in drug-of-abuse testing. J Anal Toxicol. 2012:36(7):538-539.9. Ritter D, Cortese CM, Edwards LC, et al. Interference with experimentation for lysergic mountain diethylamide. Clin Chem. 1997;43:635-637.10. Kaplan J, shah P, Faley B, Siegel ME. Instance reports the aripiprazole leading to false-positive to pee amphetamine drug displays in children. Pediatrics. 2015;136(6):e1625-e1628.11. Baden LR, Horowitz G, Jacoby H, Eliopoulos GM. Quinolones and false-positive to pee screening because that opiates through immunoassay technology. JAMA. 2001;286(24):3115-3119.12. Zacher JL, Givone DM. False-positive pee opiate screening connected with fluoroquinolone use. Ann Pharmacother. 2004;38(9):1525-1528.13. De Paula M, Saiz LC, González-Revaldería J, et al. Rifampicin causes false-positive immunoassay results for to pee opiates. Clin Chem laboratory Med. 1998;36(4):241-243.14. Kelner MJ. Positive diphenhydramine interference in the EMIT-d.a.u. Assay. Clin Chem. 1984;30:1430.15. Hausmann E, Kohl B, von Boehmer H, Wellhöner HH. False-positive EMIT indication of opiates and also methadone in a doxylamine intoxication. J Clin Chem Clin Biochem. 1983;21(10):599-600.16. Poklis A, room KV, tho J, et al. Ranitidine interfer-ence through the monoclonal EMIT d.a.u. Amphetamine/methamphetamine immunoassay. J Anal Toxicol. 1991;15(2):101-103.17. Markowitz JS, Donovan JL, DeVane CL, et al. Usual herbal supplements go not create false-positive outcomes on urine drug screens analyzed through enzyme immunoassay. J Anal Toxicol. 2004;28:272-273.18. Levisky JA, Karch SB, Bowerman DL, et al. False-positive RIA because that methamphetamine complying with ingestion of an ephedra-derived natural product. J Anal Toxicol. 2003;27(2):123-124.19. Winek CL, Elzein EO, Wahba WW, et al. Interference of organic drinks with urinalysis for drugs of abuse. J Anal Toxicol. 1993;17(4):246-247.