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

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


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

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

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Urine drug screen (UDS) trial and error can rise workplace safety, detect drug abuse, monitor patients’ compliance with prescription medications, and assess suspected medicine ingestions.1 Thus, these tests are frequently used in clinical exercise to assistance decision-making top top the use of high-risk medications. The most frequently used form of UDS is the immunoassay as result of its short cost, rapidity the results, and also simplicity that use. Immunoassays detect substances above a collection threshold using antibodies.1,2 when a valuable tool, immunoassays have negative specificity the may result in false-positive results.1-3 unanticipated results must be confirmed with a 2nd test, such together gas chromatography–mass spectrometry (GC-MS) or high-performance liquid color layer analyzer (HPLC), that is an ext accurate; however, this tests space costly and also require extra time come perform.1-3 Therefore, patient treatment decisions are regularly made based upon presumed hopeful or negative immunoassay test results.

Interpreting check Results

Misinterpretation of UDS outcomes may have adverse consequences for patients, consisting of unwarranted loss of a job, potential criminal charges, ns of qualification indigenous sporting events or rehabilitation programs, possibly improper medical treatment, or loss of to trust from medical care professionals.2,3 Patients that are forced to obtain random or recurrent UDS testing as part of rehabilitation programs; together a stipulation of employment; for wellness monitoring, such together for pain administration or medication compliance; or for other reasons room at particularly high threat of an adverse consequences from misinterpreted UDS results.1,4 to decrease the likelihood of misinterpretation, pharmacologists can assist by identifying medications at high risk for leading to false-negatives and false-positives and also choosing medications less likely to reason these inaccuracies.

False-Negatives: To assist in interpreting UDS results, pharmacists should gain a thorough list of every the patient’s prescription, OTC, and herbal drugs prior to testing, as well as discuss adherence to medications. Once a an unfavorable screening result is obtained, pharmacists should closely consider the potential because that a false-negative result, specifically for patient receiving UDS testing to assess compliance v a medicine regimen or because that those exhibiting habits or risk components suggestive of drug abuse or drug dependency.1

False-negatives can take place when the urine medicine concentration is below the threshold level collection by the activities performing the test.1,2 Dilute urine, the term of time between ingestion the the drug and also time of testing, and the amount of the drug ingested may influence the occurrence of false-negatives.1-2 while chronic marijuana usage will show in the urine for weeks after hefty use, other medications and also illicit drugs will just be present for 1 come 4 days, as displayed in TABLE 1.1-4

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Patients may purposefully effort to hide positive screening outcomes by adding contaminants to your urine that mask the presence of a drug, such as vinegar, soap, bleach, drain cleaner, eye drops, table salt, or ammonia.5 Additionally, commercial products with the active ingredients peroxide (peroxidase), glutaraldehyde, salt or potassium nitrite, and pyridinium chlorochromate can be used.5 transforms in pee appearance, color, details gravity, or pH may show the presence of a contaminant and also should it is in checked. Patients may additionally drink an extreme amount of water (2-4 qt) or use diuretics come purposefully dilute your urine and also the urine drug concentration come decrease the opportunity of detection.5,6

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

Similarly, opiates have the right to be at danger for false-negatives. Most immunoassay exam look for morphine, norcodeine, and also codeine; hence morphine, heroin, and codeine can easily be detected. Hydrocodone and hydromorphone room metabolites the codeine and also are rarely optimistic on immunoassay tests. Oxycodone, buprenorphine, and also tramadol monitor a separate metabolic pathway, and also fentanyl might not it is in detected due to the fact that it lacks metabolites.1,4 To minimization 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 also be recommended. Immunoassays test because that amphetamines; thus, amphetamine, dextroamphetamine, and also lisdexamfetamine products should return optimistic results for compliance experimentation if bring away in the critical 2 come 3 days. Illegal methamphetamine will also show hopeful within the amphetamine immunoassay test. However, methylphenidate commodities do no cross-react through amphetamines and also will frequently produce an adverse results,8 return a false-positive result with methylphenidate has actually been checked out in one pediatric situation report.1-2,8 If methylphenidate products are used, a GC-MS test need to be routinely administered.

False-Positives: In enhancement to false-negatives, pharmacists require 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 reason false-positive results with common substances the abuse or tricyclic antidepressants (TCAs).1-4 False-positives can happen when a medication has a cross-reactivity through the immunoassay, often because of a similarity in the framework of the parent medication or among its metabolites come the experiment drug.2 The incident of false-positives is mostly impacted by the kind of immunoassay used and by the details agent being tested.2

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When selecting therapeutic agents because that high-risk patients, pharmacists should consider minimizing the use of drugs well-known to reason false-positive results, if possible. The choice of an ideal therapeutic agent because that a patient counts on plenty of factors, such together the effectiveness and also adverse-effect profile of the drug; therefore, minimizing the use of medications presented to cause false-positives should be weighed against clinical referee in product selection. However, for patients undergoing constant UDS testing, picking an agent least likely to cause false-positives would certainly be crucial consideration to assist minimize adverse results to patients from perhaps misinterpreted results.

Antidepressants

Many that the drugs reported to reason false-positive UDS results encompass a selection of antidepressants, which can be used for assorted indications. The the selective serotonin reuptake inhibitors (SSRIs), sertraline has actually been report to reason false-positive outcomes for benzodiazepines and also lysergic mountain diethylamide (LSD),1-4,9 and fluoxetine has actually been report to cause false-positive outcomes for LSD and also amphetamines.1,3,9 Bupropion and trazodone have similarly been reported to cause false-positive LSD and amphetamine results, with the communication to the amphetamine assay credited to cross-reactivity with the agents’ metabolites.1-4,9 Additionally, numerous reports have found venlafaxine to cause false-positive phencyclidine (PCP) results.2-4 while both venlafaxine and its active metabolite, O-desmethylvenlafaxine, space structurally dissimilar to PCP and have incredibly low cross-reactivity (0.0125% and also 0.025%, respectively), the concentration of the two together have been hypothesized to cause the false-positive results.2,4

Furthermore, virtually all TCAs can reason false-positive UDS results. Amitriptyline, desipramine, doxepin, and also imipramine have actually been report to reason false-positive results for LSD,3 and also desipramine and doxepin have furthermore been report to cause false-positive results for amphetamines.1,2 While hardly ever used, the monoamine oxidase inhibitor (MAOI) selegiline may additionally 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 possible may diminish the hazard of false-positive results. Because that patients requiring an SSRI, pharmacologists should think about using paroxetine, citalopram, or escitalopram and minimizing the usage of fluoxetine and also sertraline once appropriate. Once using an antidepressant come treat neuropathic pain, minimizing the use of venlafaxine and also TCAs and also instead utilizing duloxetine should be considered. Gabapentin and also pregabalin have actually a minimal danger of bring about false-positives and also are other choices that could be used. Trazodone is one antidepressant generally used together a sleep aid. Minimizing that use and also instead making use of mirtazapine or sedative-hypnotics when appropriate would be one more consideration.1-4

Antipsychotics

In addition to antidepressants, many antipsychotic agents have additionally been report to reason false-positive results. Antipsychotics may be supplied to act a range of psychiatric disorders, v the second-generation antipsychotics (SGAs) used much more frequently as result of their much more favorable side-effect profile compared to the first-generation antipsychotics (FGAs). That the SGAs, risperidone has been reported to reason false-positive LSD results;3,9 quetiapine, false-positive methadone and also TCA results, which space attributed to quetiapine’s resemblance in structure to methadone and TCAs.2-4 Two situation reports of inadvertently aripiprazole sloop down in pediatric patients resulted in false-positive amphetamine results.10 even if it is false-positives with aripiprazole may also occur in adults is uncertain.10 The FGAs chlorpromazine, prochlorperazine, haloperidol, and thioridazine might all reason false-positive LSD results.3 Thioridazine may additionally 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 choosing an antipsychotic agent because that high-risk patients, factor to consider should be given to making use of lurasidone, olanzapine, or ziprasidone when appropriate. Aripiprazole may additionally be a reasonable choice in adults, as no reports have uncovered false-positive results in this population. However, pharmacologists should closely consider the opportunity of a positive result being false must one happen with a patient on aripiprazole. Numerous of the FGAs cause false-positive UDS results and have a much less favorable side-effect profile compared to the SGAs; thus, minimizing usage of these agents when feasible would it is in suggested.1-4

Other main Nervous device (CNS) Medications

Other CNS agents that have been report to reason false-positive UDS results include buspirone, carbamazepine, and also lamotrigine (TABLE 2).1-4 Minimizing use of these agents when feasible can also assist reduce the threat of false-positive results.

Antiemetics

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

Antibiotics

Most antibiotics have actually not been indicated to reason false-positives with UDS immunoassays; however, quinolones and also rifampin have been documented in little studies.4 all quinolones have the potential to cause a false-positive opiate screening result, with levofloxacin and also ofloxacin having actually the greatest risk. Ciprofloxacin, moxifloxacin, and norfloxacin showed cross-reactivity come opiates since of similar molecular structures, yet at reduced levels than most immunoassay thresholds. Thus, these agents may be less likely to reason false-positives.4,11-12 Ofloxacin has likewise been report to cause a false-positive amphetamine result.3 In enhancement to quinolones, rifampin has been presented to reason false-positives because that opioids, and elimination calculations calculation a possible false-positive an outcome for more than 18 hours after a single oral dose of rifampin 600 mg.13

OTCs

Determining what OTC assets patients room taking is really important once using UDS testing, as part OTCs may cause false-positive results. Antihistamines, analgesics, sneeze suppressants, and heartburn medications have actually been displayed to reason false-positives in studies and also case reports.1-4

False-positive methadone levels have been documented with diphenhydramine 100 to 200 mg2-4,14 and also doxylamine intoxication.4,15 Additionally, doxylamine intoxication has developed false-positive opiate14 and PCP2 levels, and also brompheniramine usage may reason false-positive amphetamine4 and LSD3,9 levels. Consider using second-generation antihistamines, together they have not been reported to reason false-positive UDS results.

Nonsteroidal anti-inflammatory medicine (NSAIDs) have likewise been displayed to connect with UDS immunoassays. Both ibuprofen and naproxen have been documented to reason false-positive barbiturate4 and cannabinoid1-4 levels. In addition, ibufrofen can cause a false-positive PCP level.1-2,4 take into consideration minimizing the usage of NSAIDs in high-risk patients and also recommending acetaminophen instead.

The sneeze suppressant dextromethorphan may cause false-positive PCP1,2,4 and opioid levels because of its metabolite’s similarity to the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have displayed false-positive amphetamine levels due to comparable structures.1,2 To avoid misinterpretations, think about limiting these drugs in high-risk populations.

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

Herbals

Herbal products may also interfere v UDS immunoassays. Together morphine and also codeine are derived from opium poppy seeds, the intake of fairly small amounts of poppy seed may result in false-positives because that opiates, consisting of the usage of poppy-seed cookies (having ~1 tsp that poppy-seed filling) or poppy-seed bagels.2 Additionally, the gulp down of foods items containing hemp, such together hemp-seed oil, have resulted in positive marijuana UDS results,2 and ephedra-containing commodities may reason false-positive methamphetamine results.17

Other herbal supplements might be less likely to cause false-positive check results. A study of gingko biloba, experienced palmetto, St. John’s wort, ginseng, garlic, green tea, valerian, and also cranberry did no cause any false-positive reactions.18 Similarly, herbal teas and drinks did not cause any false-positives.19 carefully assessing patient usage of these products can help minimize misinterpretation the UDS results.

Conclusion

By recognizing typical causes and medication involves for false-negatives and also false-positives in UDS testing, pharmacists can improve care and provide insight into different medications because that patients. In every cases, clinical judgment have to be offered in choosing an suitable therapeutic agent. Unexpected outcomes from a UDS immunoassay need to be checked v a confirmatory GC-MS or HPLC test. By reduce medication-related reasons of false-positives and false-negatives, pharmacists can potentially diminish the need for additional testing and also the an unfavorable consequences the misinterpreted to pee immunoassay testing, therefore optimizing patience care.

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REFERENCES

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