Alyson Schwebach, PharmD Candidate 2016Student PharmacistSouth Dakota State UniversityCollege the PharmacyBrookings, southern Dakota
Jennifer Ball, PharmDAssistant Professor the Pharmacy PracticeSouth Dakota State UniversityCollege that PharmacyBrookings, southern DakotaClinical Pharmacist, facility for family MedicineAdjunct Assistant Professor of family MedicineUniversity of south Dakota college of MedicineSioux Falls, south Dakota
US Pharm. 2016;41(8):26-30.
ABSTRACT: Urine drug screening is a common means to test for compliance through medications having actually high abuse potential. False-negatives and false-positives from immunoassays have the right to lead come adverse after-effects for patients and also providers. By identifying medicines that add to false-negatives and also false-positives, pharmacologists decrease misinterpretations native urine drug screens. Unexpected results from pee immunoassays should have a confirmatory gas chromatography–mass spectrometry or a high-performance liquid chromatography test performed. Pharmacists can administer guidance in selecting proper drug therapies that are less likely to cause false readings, thus decreasing the require for added testing.
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Urine drug screen (UDS) experimentation can increase workplace safety, detect medicine abuse, screen patients’ compliance through prescription medications, and assess suspected medicine ingestions.1 Thus, these tests are generally used in clinical exercise to assistance decision-making top top the use of high-risk medications. The most commonly used form of UDS is the immunoassay because of its short cost, rapidity of results, and simplicity that use. Immunoassays detect substances above a set threshold using antibodies.1,2 if a useful tool, immunoassays have negative specificity that may bring about false-positive results.1-3 unanticipated results must be shown with a second test, such as gas chromatography–mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC), that is more accurate; however, this tests are costly and require extra time come perform.1-3 Therefore, patient treatment decisions are often made based on presumed confident or an unfavorable immunoassay check results.
Interpreting check Results
Misinterpretation of UDS results may have adverse consequences for patients, including unwarranted ns of a job, potential criminal charges, loss of qualification indigenous sporting occasions or rehabilitation programs, perhaps improper clinical treatment, or loss of to trust from medical care professionals.2,3 Patients who are compelled to receive random or recurrent UDS testing as part of rehabilitation programs; as a stipulation that employment; for wellness monitoring, such together for pain monitoring or medicine compliance; or for various other reasons room at particularly high threat of negative consequences from misinterpreted UDS results.1,4 come decrease the likelihood the misinterpretation, pharmacists can help by identifying drugs at high hazard for causing false-negatives and also false-positives and also choosing medications much less likely to reason these inaccuracies.
False-Negatives: To assist in interpreting UDS results, pharmacists should obtain a thorough list of every the patient’s prescription, OTC, and also herbal drugs prior to testing, as well as discuss adherence to medications. As soon as a an adverse screening result is obtained, pharmacists should very closely consider the potential because that a false-negative result, specifically for patient receiving UDS experimentation to evaluate compliance through a medicine regimen or because that those exhibiting behaviors or risk factors suggestive of medicine abuse or drug dependency.1
False-negatives can happen when the urine medicine concentration is listed below the threshold level collection by the activities performing the test.1,2 Dilute urine, the term of time between ingestion that the drug and also time that testing, and also the amount of the drug ingested may influence the incident of false-negatives.1-2 when chronic marijuana usage will display in the urine because that weeks after heavy use, various other medications and illicit drugs will just be present for 1 come 4 days, as presented in TABLE 1.1-4
Patients may purposefully attempt to hide hopeful screening outcomes by adding contaminants to your urine the mask the existence of a drug, such together vinegar, soap, bleach, drain cleaner, eye drops, table salt, or ammonia.5 Additionally, commercial products with the active ingredients peroxide (peroxidase), glutaraldehyde, sodium or potassium nitrite, and also pyridinium chlorochromate might be used.5 transforms in to pee appearance, color, specific gravity, or pH may show the existence of a contaminant and also should be checked. Patient may likewise drink an too much amount the water (2-4 qt) or use diuretics to purposefully dilute your urine and also the urine medicine concentration come decrease the possibility of detection.5,6
Furthermore, false-negatives may additionally occur because the UDS is merely unable come detect the agent. For example, UDS tests for benzodiazepines commonly result in false-negatives because that agents the have negative cross-reactivity through the assay.7 most assays because that benzodiazepines recognize their presence in the pee by trial and error for nordiazepam and oxazepam, the main metabolites of many benzodiazepines.2 Agents the follow a different metabolic pathway, such together triazolam, alprazolam, clonazepam, and lorazepam, have poor cross-reactivity v the assay as result of the lack of these metabolites and thus commonly produce false-negative results.2,7 Therefore, come decrease the require for confirmatory testing, diazepam, oxazepam, and also temazepam might be preferred.
Similarly, opiates deserve to be at danger for false-negatives. Most immunoassay test look because that morphine, norcodeine, and codeine; therefore morphine, heroin, and also codeine can easily be detected. Hydrocodone and also hydromorphone space metabolites the codeine and are rarely hopeful on immunoassay tests. Oxycodone, buprenorphine, and also tramadol follow a separate metabolic pathway, and also fentanyl may not it is in detected due to the fact that it lacks metabolites.1,4 To minimize the require for confirmatory testing, take into consideration using morphine or codeine in high-risk patients.
For patients gift treated because that attention-deficit/hyperactivity disorder (ADHD), UDS trial and error may additionally be recommended. Immunoassays test because that amphetamines; thus, amphetamine, dextroamphetamine, and also lisdexamfetamine commodities should return optimistic results for compliance trial and error if taken in the last 2 to 3 days. Illegal methamphetamine will also show confident within the amphetamine immunoassay test. However, methylphenidate products do not cross-react through amphetamines and will generally produce an unfavorable results,8 back a false-positive result with methylphenidate has actually been watched in one pediatric instance report.1-2,8 If methylphenidate products are used, a GC-MS test have to be routinely administered.
False-Positives: In enhancement to false-negatives, pharmacists need to take into consideration the potential for false-positive UDS results and be mindful of drugs that may reason false-positives. TABLE 2 summarizes countless medications that have been report to cause false-positive outcomes with typical substances that abuse or tricyclic antidepressants (TCAs).1-4 False-positives can take place when a medication has actually a cross-reactivity with the immunoassay, often due to a similarity in the framework of the parental medication or among its metabolites come the tested drug.2 The occurrence of false-positives is mostly impacted by the form of immunoassay used and also by the specific agent gift tested.2
When picking therapeutic agents for high-risk patients, pharmacologists should think about minimizing the use of drugs known to cause false-positive results, if possible. The an option of an ideal therapeutic agent for a patient depends on plenty of factors, such as the effectiveness and adverse-effect profile of the drug; therefore, minimizing the use of medications shown to reason false-positives need to be weighed against clinical judgment in product selection. However, for patients undergoing regular UDS testing, choosing an agent least likely to cause false-positives would be an important consideration to assist minimize adverse results to patient from perhaps misinterpreted results.
Many of the medicines reported to reason false-positive UDS results encompass a selection of antidepressants, which have the right to be supplied for assorted indications. That the selective serotonin reuptake inhibitors (SSRIs), sertraline has actually been reported to cause false-positive outcomes for benzodiazepines and lysergic mountain diethylamide (LSD),1-4,9 and also fluoxetine has been report to cause false-positive results for LSD and also amphetamines.1,3,9 Bupropion and trazodone have an in similar way been report to reason false-positive LSD and amphetamine results, through the communication to the amphetamine assay attributed to cross-reactivity v the agents’ metabolites.1-4,9 Additionally, countless reports have uncovered venlafaxine to reason false-positive phencyclidine (PCP) results.2-4 when both venlafaxine and its active metabolite, O-desmethylvenlafaxine, are structurally dissimilar come PCP and have extremely low cross-reactivity (0.0125% and 0.025%, respectively), the concentration of the two together have been hypothesized to reason the false-positive results.2,4
Furthermore, virtually all TCAs can reason false-positive UDS results. Amitriptyline, desipramine, doxepin, and imipramine have been report to cause false-positive outcomes for LSD,3 and also desipramine and also doxepin have in addition been report to reason false-positive outcomes for amphetamines.1,2 While rarely used, the monoamine oxidase inhibitor (MAOI) selegiline may also cause false-positive amphetamine results because of its l-amphetamine and also l-methamphetamine metabolites.2,4
Minimizing the usage of this agents in high-risk patient when possible may decrease the threat of false-positive results. Because that patients inquiry an SSRI, pharmacologists should think about using paroxetine, citalopram, or escitalopram and also minimizing the usage of fluoxetine and also sertraline as soon as appropriate. Once using an antidepressant come treat neuropathic pain, minimizing the usage of venlafaxine and also TCAs and also instead making use of duloxetine need to be considered. Gabapentin and pregabalin have a minimal danger of resulting in false-positives and are other options that could be used. Trazodone is an antidepressant commonly used as a sleep aid. Minimizing that is use and instead utilizing mirtazapine or sedative-hypnotics when ideal would be another consideration.1-4
In enhancement to antidepressants, many antipsychotic agents have likewise been reported to cause false-positive results. Antipsychotics might be supplied to treat a variety of psychiatric disorders, with the second-generation antipsychotics (SGAs) used an ext frequently as result of their an ext favorable side-effect profile compared to the first-generation antipsychotics (FGAs). Of the SGAs, risperidone has been reported to cause false-positive LSD results;3,9 quetiapine, false-positive methadone and also TCA results, which room attributed come quetiapine’s resemblance in framework to methadone and TCAs.2-4 Two situation reports of inadvertently aripiprazole gulp down in pediatric patients caused false-positive amphetamine results.10 whether false-positives through aripiprazole may also occur in adult is uncertain.10 The FGAs chlorpromazine, prochlorperazine, haloperidol, and also thioridazine may all cause false-positive LSD results.3 Thioridazine may furthermore cause false-positive amphetamine, methadone, and PCP results, and chlorpromazine reason false-positive amphetamine (due to similarities in structure) and methadone results.1-4
When picking an antipsychotic agent because that high-risk patients, consideration should be offered to utilizing lurasidone, olanzapine, or ziprasidone as soon as appropriate. Aripiprazole may likewise be a reasonable alternative in adults, together no reports have found false-positive results in this population. However, pharmacists should carefully consider the possibility of a positive result being false need to one take place with a patience on aripiprazole. Many of the FGAs cause false-positive UDS results and also have a less favorable side-effect profile contrasted 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 reason false-positive UDS results encompass buspirone, carbamazepine, and also lamotrigine (TABLE 2).1-4 Minimizing use of this agents when feasible can also assist reduce the risk of false-positive results.
In addition to the antiemetics promethazine and also doxylamine, metoclopramide and prochlorperazine have had documented false-positive LSD results.3 think about minimizing the usage of this agents and also selecting 5-HT3 receptor antagonists such together ondansetron come decrease false readings in high-risk populations.3
Most antibiotics have not been suggested to reason false-positives through UDS immunoassays; however, quinolones and also rifampin have actually been documented in small studies.4 every quinolones have actually the potential to cause a false-positive opiate screening result, through levofloxacin and ofloxacin having the highest possible risk. Ciprofloxacin, moxifloxacin, and also norfloxacin verified cross-reactivity to opiates due to the fact that of similar molecular structures, yet at lower levels than most immunoassay thresholds. Thus, this agents may be much less likely to cause false-positives.4,11-12 Ofloxacin has likewise been reported to cause a false-positive amphetamine result.3 In addition to quinolones, rifampin has actually been shown to cause false-positives for opioids, and also elimination calculations estimate a possible false-positive result for more than 18 hrs after a solitary oral sheep of rifampin 600 mg.13
Determining what OTC products patients are taking is really important once using UDS testing, as some OTCs may cause false-positive results. Antihistamines, analgesics, cough suppressants, and heartburn medications have been displayed to cause false-positives in studies and also case reports.1-4
False-positive methadone levels have been recorded with diphenhydramine 100 come 200 mg2-4,14 and also doxylamine intoxication.4,15 Additionally, doxylamine intoxication has produced false-positive opiate14 and PCP2 levels, and also brompheniramine usage may reason false-positive amphetamine4 and also LSD3,9 levels. Take into consideration using second-generation antihistamines, as they have actually not been reported to reason false-positive UDS results.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been displayed to communicate with UDS immunoassays. Both ibuprofen and also naproxen have actually been documented to reason false-positive barbiturate4 and cannabinoid1-4 levels. In addition, ibufrofen can reason a false-positive PCP level.1-2,4 think about minimizing the use of NSAIDs in high-risk patients and also recommending paracetamol instead.
The sneeze suppressant dextromethorphan may reason false-positive PCP1,2,4 and opioid levels due to its metabolite’s similarity come the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have shown false-positive amphetamine level due to similar structures.1,2 To stop misinterpretations, take into consideration limiting these medicines in high-risk populations.
Lastly, heartburn medications have been documented to connect with UDS exam to reason false-positives. Ranitidine has actually been presented to cause false-positive outcomes for amphetamines at doses of 150 come 300 mg daily.16 top top the various other hand, pantoprazole has 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 presented to cause false-positives.
Herbal products may likewise interfere through UDS immunoassays. As morphine and also codeine are derived from opium poppy seeds, the input of relatively small amounts of poppy seeds may result in false-positives because that opiates, including the consumption of poppy-seed cookie (having ~1 tsp that poppy-seed filling) or poppy-seed bagels.2 Additionally, the sloop down of foodstuffs containing hemp, such as hemp-seed oil, have actually resulted in optimistic marijuana UDS results,2 and also ephedra-containing commodities may cause false-positive methamphetamine results.17
Other organic supplements may be less likely to cause false-positive test results. A examine of gingko biloba, saw palmetto, St. John’s wort, ginseng, garlic, eco-friendly tea, valerian, and also cranberry did no cause any type of false-positive reactions.18 Similarly, organic teas and also drinks did not cause any false-positives.19 carefully assessing patient usage of these products can assist minimize misinterpretation that UDS results.
By recognizing usual causes and also medication pertains to for false-negatives and false-positives in UDS testing, pharmacists have the right to improve care and administer insight into alternate medications for patients. In every cases, clinical judgment should be provided in choosing an proper therapeutic agent. Unexpected results from a UDS immunoassay need to be checked with a confirmatory GC-MS or HPLC test. By reducing medication-related reasons of false-positives and also false-negatives, pharmacists deserve to potentially to decrease the require for extr testing and the negative consequences of misinterpreted to pee immunoassay testing, for this reason optimizing patience care.
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1. Standridge JB, Adams SM, Zotos AP. Urine medicine screening: a beneficial office procedure. Am Fam Physician. 2010;81(5):635-640.2. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76.3. Saitman A, Park HD, Fitzgerald RL. False-positive interferences of typical urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387-396.4. Brahm NC, Yeager LL, Fox MD, et al. Commonly prescribed medications and potential false-positive urine drug screens. To be J wellness Syst Pharm. 2010;67(16):1344-1350.5. Jaffee WB, Trucco E, levy S, Weiss RD. Is this urine yes, really negative? A systematic review of tampering techniques 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 liquid ingestion reasons false-negative marijuana and also cocaine urine check results. J Anal Toxicol. 1998;22(6):460-473.7. Johnson-Davis KL, Sadler AJ, Genzen JR. A retrospective evaluation of urine drugs of abuse immunoassay true hopeful rates at a national reference library. J Anal Toxicol. 2016;40(2):97-107.8. Breindahl T, Hindersson P. Methylphenidate is differentiated 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 acid diethylamide. Clin Chem. 1997;43:635-637.10. Kaplan J, shah P, Faley B, Siegel ME. Situation reports the aripiprazole causing false-positive pee amphetamine drug display screens in children. Pediatrics. 2015;136(6):e1625-e1628.11. Baden LR, Horowitz G, Jacoby H, Eliopoulos GM. Quinolones and also false-positive to pee screening because that opiates by immunoassay technology. JAMA. 2001;286(24):3115-3119.12. Zacher JL, Givone DM. False-positive urine 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 reasons false-positive immunoassay results for to pee opiates. Clin Chem lab Med. 1998;36(4):241-243.14. Kelner MJ. Confident 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 point out of opiates and 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 v 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. Common herbal supplements go not produce false-positive results on to pee drug display screens analyzed through enzyme immunoassay. J Anal Toxicol. 2004;28:272-273.18. Levisky JA, Karch SB, Bowerman DL, et al. False-positive RIA for methamphetamine complying with ingestion of one ephedra-derived organic product. J Anal Toxicol. 2003;27(2):123-124.19. Winek CL, Elzein EO, Wahba WW, et al. Interference of herbal drinks through urinalysis because that drugs of abuse. J Anal Toxicol. 1993;17(4):246-247.