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

Abstract: Urine drug screening is a common mode to exam for compliance with medications having high abuse potential. False-negatives and simulated-positives from immunoassays can atomic number 82 to adverse consequences for patients and providers. Past identifying medications that contribute to imitation-negatives and false-positives, pharmacists decrease misinterpretations from urine drug screens. Unexpected results from urine immunoassays should have a confirmatory gas chromatography–mass spectrometry or a high-operation liquid chromatography test performed. Pharmacists can provide guidance in selecting advisable drug therapies that are less likely to cause false readings, thus decreasing the need for additional testing.

Urine drug screen (UDS) testing tin increase workplace safety, detect drug abuse, monitor patients' compliance with prescription medications, and appraise suspected drug ingestions.1 Thus, these tests are normally used in clinical practice to support determination-making on the utilize of high-gamble medications. The near ofttimes used blazon of UDS is the immunoassay due to its low toll, rapidity of results, and simplicity of utilise. Immunoassays detect substances above a set threshold using antibodies.ane,2 While a useful tool, immunoassays take poor specificity that may lead to false-positive results.1-three Unexpected results should be confirmed with a 2d exam, such as gas chromatography–mass spectrometry (GC-MS) or loftier-performance liquid chromatography (HPLC), that is more accurate; even so, these tests are costly and require extra time to perform.1-3 Therefore, patient care decisions are oftentimes made based on presumed positive or negative immunoassay test results.

Interpreting Test Results

Misinterpretation of UDS results may have adverse consequences for patients, including unwarranted loss of a job, potential criminal charges, loss of qualification from sporting events or rehabilitation programs, potentially improper medical handling, or loss of trust from healthcare professionals.2,3 Patients who are required to receive random or recurrent UDS testing equally role of rehabilitation programs; as a stipulation of employment; for wellness monitoring, such as for hurting direction or medication compliance; or for other reasons are at especially high risk of negative consequences from misinterpreted UDS results.one,4 To decrease the likelihood of misinterpretation, pharmacists can assist by identifying medications at high run a risk for causing false-negatives and imitation-positives and choosing medications less likely to cause these inaccuracies.

False-Negatives: To help in interpreting UDS results, pharmacists should learn a thorough list of all the patient's prescription, OTC, and herbal medications prior to testing, as well every bit talk over adherence to medications. When a negative screening event is obtained, pharmacists should carefully consider the potential for a false-negative result, specially for patients receiving UDS testing to assess compliance with a medication regimen or for those exhibiting behaviors or risk factors suggestive of drug abuse or drug dependency.i

Simulated-negatives tin can occur when the urine drug concentration is below the threshold level gear up by the laboratory performing the test.1,ii Dilute urine, the elapsing of time between ingestion of the drug and time of testing, and the quantity of the drug ingested may affect the occurrence of false-negatives.one-2 While chronic marijuana use will show in the urine for weeks after heavy utilise, other medications and illicit drugs volition but be nowadays for 1 to 4 days, equally shown in TABLE 1.1-four

Patients may purposefully endeavour to hibernate positive screening results by adding contaminants to their urine that mask the presence of a drug, such as vinegar, soap, bleach, drain cleaner, eye drops, tabular array salt, or ammonia.5 Additionally, commercial products with the active ingredients peroxide (peroxidase), glutaraldehyde, sodium or potassium nitrite, and pyridinium chlorochromate could exist used.five Changes in urine appearance, colour, specific gravity, or pH may indicate the presence of a contaminant and should be checked. Patients may also drink an excessive amount of h2o (2-four qt) or use diuretics to purposefully dilute their urine and the urine drug concentration to subtract the chance of detection.5,six

Furthermore, false-negatives may also occur because the UDS is simply unable to detect the amanuensis. For example, UDS tests for benzodiazepines commonly effect in false-negatives for agents that accept poor cross-reactivity with the analysis.7 Almost assays for benzodiazepines find their presence in the urine by testing for nordiazepam and oxazepam, the master metabolites of about benzodiazepines.ii Agents that follow a different metabolic pathway, such as triazolam, alprazolam, clonazepam, and lorazepam, take poor cross-reactivity with the analysis due to the absence of these metabolites and thus frequently produce false-negative results.two,7 Therefore, to decrease the demand for confirmatory testing, diazepam, oxazepam, and temazepam may be preferred.

Similarly, opiates tin exist at take chances for simulated-negatives. Most immunoassay tests look for morphine, norcodeine, and codeine; thus morphine, heroin, and codeine can hands be detected. Hydrocodone and hydromorphone are metabolites of codeine and are rarely positive on immunoassay tests. Oxycodone, buprenorphine, and tramadol follow a separate metabolic pathway, and fentanyl may non be detected considering it lacks metabolites.1,4 To minimize the need for confirmatory testing, consider using morphine or codeine in high-risk patients.

For patients existence treated for attention-arrears/hyperactivity disorder (ADHD), UDS testing may too be recommended. Immunoassays test for amphetamines; thus, amphetamine, dextroamphetamine, and lisdexamfetamine products should return positive results for compliance testing if taken in the terminal 2 to iii days. Illicit methamphetamine volition also show positive within the amphetamine immunoassay test. However, methylphenidate products practise not cross-react with amphetamines and will unremarkably produce negative results,8 although a false-positive result with methylphenidate has been seen in one pediatric case written report.i-2,8 If methylphenidate products are used, a GC-MS exam should be routinely administered.

Imitation-Positives: In addition to false-negatives, pharmacists need to consider the potential for false-positive UDS results and be aware of medications that may cause false-positives. Table ii summarizes many medications that have been reported to crusade false-positive results with common substances of abuse or tricyclic antidepressants (TCAs).1-4 Faux-positives can occur when a medication has a cantankerous-reactivity with the immunoassay, oftentimes due to a similarity in the structure of the parent medication or one of its metabolites to the tested drug.ii The occurrence of imitation-positives is mostly affected past the type of immunoassay used and past the particular amanuensis beingness tested.2

When selecting therapeutic agents for loftier-risk patients, pharmacists should consider minimizing the use of drugs known to cause false-positive results, if possible. The selection of an appropriate therapeutic amanuensis for a patient depends on numerous factors, such as the effectiveness and adverse-issue contour of the drug; therefore, minimizing the use of medications shown to cause false-positives must be weighed against clinical judgment in product selection. However, for patients undergoing frequent UDS testing, selecting an agent least likely to cause false-positives would exist an of import consideration to help minimize adverse consequences to patients from potentially misinterpreted results.

Antidepressants

Many of the medications reported to cause false-positive UDS results include a variety of antidepressants, which can be used for various indications. Of the selective serotonin reuptake inhibitors (SSRIs), sertraline has been reported to crusade simulated-positive results for benzodiazepines and lysergic acid diethylamide (LSD),1-4,9 and fluoxetine has been reported to cause false-positive results for LSD and amphetamines.i,3,9 Bupropion and trazodone have too been reported to crusade false-positive LSD and amphetamine results, with the interaction to the amphetamine assay credited to cross-reactivity with the agents' metabolites.1-4,nine Additionally, numerous reports accept plant venlafaxine to cause false-positive phencyclidine (PCP) results.ii-4 While both venlafaxine and its active metabolite, O-desmethylvenlafaxine, are structurally different to PCP and 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,four

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

Minimizing the utilize of these agents in loftier-take a chance patients when possible may decrease the risk of faux-positive results. For patients requiring an SSRI, pharmacists should consider using paroxetine, citalopram, or escitalopram and minimizing the utilize of fluoxetine and sertraline when appropriate. When using an antidepressant to treat neuropathic hurting, minimizing the use of venlafaxine and TCAs and instead using duloxetine should exist considered. Gabapentin and pregabalin accept a minimal gamble of causing faux-positives and are other options that could exist used. Trazodone is an antidepressant frequently used as a slumber aid. Minimizing its use and instead using mirtazapine or sedative-hypnotics when appropriate would be some other consideration.1-iv

Antipsychotics

In addition to antidepressants, many antipsychotic agents have also 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 more frequently due to their more favorable side-effect contour compared to the first-generation antipsychotics (FGAs). Of the SGAs, risperidone has been reported to cause imitation-positive LSD results;3,9 quetiapine, false-positive methadone and TCA results, which are attributed to quetiapine's resemblance in structure to methadone and TCAs.ii-iv 2 case reports of accidental aripiprazole ingestion in pediatric patients resulted in false-positive amphetamine results.x Whether false-positives with aripiprazole may also occur in adults is uncertain.ten The FGAs chlorpromazine, prochlorperazine, haloperidol, and thioridazine may all cause false-positive LSD results.iii Thioridazine may additionally crusade false-positive amphetamine, methadone, and PCP results, and chlorpromazine crusade false-positive amphetamine (due to similarities in structure) and methadone results.i-iv

When selecting an antipsychotic agent for high-take chances patients, consideration should exist given to using lurasidone, olanzapine, or ziprasidone when appropriate. Aripiprazole may too exist a reasonable option in adults, as no reports have plant false-positive results in this population. Nonetheless, pharmacists should advisedly consider the possibility of a positive effect existence fake should one occur with a patient on aripiprazole. Many of the FGAs cause imitation-positive UDS results and have a less favorable side-effect contour compared to the SGAs; thus, minimizing utilise of these agents when possible would be suggested.1-4

Other Central Nervous System (CNS) Medications

Other CNS agents that have been reported to cause false-positive UDS results include buspirone, carbamazepine, and lamotrigine (Tabular array 2).1-iv Minimizing use of these agents when possible can also help reduce the hazard of fake-positive results.

Antiemetics

In add-on to the antiemetics promethazine and doxylamine, metoclopramide and prochlorperazine have had documented false-positive LSD results.3 Consider minimizing the use of these agents and selecting 5-HTiii receptor antagonists such equally ondansetron to decrease fake readings in high-run a risk populations.3

Antibiotics

Most antibiotics have not been indicated to cause false-positives with UDS immunoassays; however, quinolones and rifampin have been documented in small studies.four All quinolones have the potential to cause a fake-positive opiate screening upshot, with levofloxacin and ofloxacin having the highest gamble. Ciprofloxacin, moxifloxacin, and norfloxacin showed cross-reactivity to opiates because of similar molecular structures, only at lower levels than almost immunoassay thresholds. Thus, these agents may be less likely to crusade simulated-positives.iv,11-12 Ofloxacin has likewise been reported to cause a false-positive amphetamine result.3 In addition to quinolones, rifampin has been shown to crusade simulated-positives for opioids, and elimination calculations estimate a possible faux-positive event for more than 18 hours afterward a single oral dose of rifampin 600 mg.13

OTCs

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

False-positive methadone levels have been documented with diphenhydramine 100 to 200 mgtwo-4,14 and doxylamine intoxication.iv,xv Additionally, doxylamine intoxication has produced simulated-positive opiatefourteen and PCP2 levels, and brompheniramine use may cause simulated-positive amphetamine4 and LSD3,9 levels. Consider using second-generation antihistamines, as they have not been reported to cause false-positive UDS results.

Nonsteroidal anti-inflammatory drugs (NSAIDs) accept besides been shown to interact with UDS immunoassays. Both ibuprofen and naproxen accept been documented to cause imitation-positive barbiturate4 and cannabinoid1-4 levels. In addition, ibuprofen tin can crusade a false-positive PCP level.1-2,4 Consider minimizing the use of NSAIDs in loftier-take a chance patients and recommending acetaminophen instead.

The coughing suppressant dextromethorphan may cause false-positive PCP1,2,4 and opioid levels due to its metabolite'south similarity to the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have shown false-positive amphetamine levels due to similar structures.ane,2 To prevent misinterpretations, consider limiting these medications in loftier-risk populations.

Lastly, heartburn medications have been documented to interact with UDS tests to cause false-positives. Ranitidine has been shown to cause false-positive results for amphetamines at doses of 150 to 300 mg daily.16 On the other manus, pantoprazole has caused false cannabinoid results.1,two Consider using other histamine blockers (eastward.thou., famotidine) or proton pump inhibitors (eastward.g., omeprazole, esomeprazole, lansoprazole) not shown to cause false-positives.

Herbals

Herbal products may also interfere with UDS immunoassays. As morphine and codeine are derived from opium poppy seeds, the intake of relatively small amounts of poppy seeds may upshot in false-positives for opiates, including the consumption of poppy-seed cookies (having ~i tsp of poppy-seed filling) or poppy-seed bagels.2 Additionally, the ingestion of foods containing hemp, such as hemp-seed oil, have resulted in positive marijuana UDS results,2 and ephedra-containing products may cause false-positive methamphetamine results.17

Other herbal supplements may be less likely to cause imitation-positive test results. A study of gingko biloba, saw palmetto, St. John'due south wort, ginseng, garlic, green tea, valerian, and cranberry did not crusade any false-positive reactions.xviii Similarly, herbal teas and drinks did not crusade any false-positives.19 Carefully assessing patient utilise of these products can help minimize misinterpretation of UDS results.

Decision

By recognizing common causes and medication concerns for false-negatives and simulated-positives in UDS testing, pharmacists can amend care and provide insight into alternative medications for patients. In all cases, clinical judgment should be used in selecting an appropriate therapeutic agent. Unexpected results from a UDS immunoassay should be checked with a confirmatory GC-MS or HPLC test. By reducing medication-related causes of false-positives and false-negatives, pharmacists can potentially decrease the need for additional testing and the negative consequences of misinterpreted urine immunoassay testing, thus optimizing patient care.

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