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

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


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

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

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Urine drug screen (UDS) experimentation can increase workplace safety, detect medicine abuse, screen patients’ compliance v prescription medications, and also assess suspected medicine ingestions.1 Thus, this tests are frequently used in clinical exercise to support decision-making ~ above the usage of high-risk medications. The most generally used type of UDS is the immunoassay as result of its low cost, rapidity of results, and also simplicity of use. Immunoassays finding substances over a collection threshold utilizing antibodies.1,2 when a valuable tool, immunoassays have negative specificity that may bring about false-positive results.1-3 unanticipated results should be evidenced with a second test, such as gas chromatography–mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC), the is much more accurate; however, this tests are costly and also require extra time come perform.1-3 Therefore, patient treatment decisions are frequently made based upon presumed optimistic or an unfavorable immunoassay test results.

Interpreting test Results

Misinterpretation the UDS outcomes may have actually adverse consequences for patients, consisting of unwarranted lose of a job, potential criminal charges, loss of qualification indigenous sporting occasions or rehabilitation programs, perhaps improper clinical treatment, or ns of trust from medical care professionals.2,3 Patients that are required to receive random or recurrent UDS experimentation 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 space at particularly high risk of negative consequences indigenous misinterpreted UDS results.1,4 come decrease the likelihood of misinterpretation, pharmacologists can help by identifying drugs at high danger for resulting in false-negatives and also false-positives and also choosing medications less likely to cause these inaccuracies.

False-Negatives: To assist in interpreting UDS results, pharmacologists should gain a thorough perform of all the patient’s prescription, OTC, and also herbal drugs prior to testing, and discuss follow to medications. Once a an adverse screening an outcome is obtained, pharmacologists should closely consider the potential for a false-negative result, especially for patient receiving UDS testing to evaluate compliance with a medicine regimen or because that those exhibiting behaviors or risk determinants suggestive of drug abuse or drug dependency.1

False-negatives can occur when the urine medicine concentration is below the threshold level set by the activities performing the test.1,2 Dilute urine, the duration of time in between ingestion of the drug and also time of testing, and also the amount of the drug ingested may impact the event of false-negatives.1-2 when chronic marijuana use will show in the urine for weeks after hefty use, various other medications and illicit drugs will just be current for 1 come 4 days, as presented in TABLE 1.1-4

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Patients may purposefully attempt to hide confident screening outcomes by including contaminants to your urine the mask the presence of a drug, such as vinegar, soap, bleach, drain cleaner, eye drops, table salt, or ammonia.5 Additionally, commercial commodities with the active ingredients peroxide (peroxidase), glutaraldehyde, sodium or potassium nitrite, and also pyridinium chlorochromate can be used.5 transforms in to pee appearance, color, particular gravity, or pH may suggest the visibility of a contaminant and also should be checked. Patient may additionally drink an extreme amount that water (2-4 qt) or use diuretics come purposefully dilute their urine and the urine medicine concentration to decrease the chance of detection.5,6

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

Similarly, opiates can be at danger for false-negatives. Many immunoassay exam look for morphine, norcodeine, and also codeine; hence morphine, heroin, and also codeine can conveniently be detected. Hydrocodone and hydromorphone space metabolites of codeine and also are rarely positive on immunoassay tests. Oxycodone, buprenorphine, and also tramadol follow a separate metabolic pathway, and also fentanyl may not it is in detected because it lacks metabolites.1,4 To minimize the require for confirmatory testing, consider using morphine or codeine in high-risk patients.

For patients gift treated for attention-deficit/hyperactivity disorder (ADHD), UDS testing may likewise be recommended. Immunoassays test because that amphetamines; thus, amphetamine, dextroamphetamine, and lisdexamfetamine commodities should return positive results because that compliance trial and error if taken in the critical 2 to 3 days. Illicit methamphetamine will also show confident within the amphetamine immunoassay test. However, methylphenidate commodities do no cross-react through amphetamines and will commonly produce an unfavorable results,8 although a false-positive an outcome with methylphenidate has been watched in one pediatric instance 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 because that false-positive UDS results and also be aware of medications that may reason false-positives. TABLE 2 summarizes numerous medications that have been reported to cause false-positive outcomes with typical substances that abuse or tricyclic antidepressants (TCAs).1-4 False-positives can happen when a medication has a cross-reactivity through the immunoassay, often as result of a similarity in the structure of the parent medication or one of its metabolites come the tested drug.2 The occurrence of false-positives is mostly impacted by the form of immunoassay used and by the particular agent being tested.2

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When picking therapeutic agents for high-risk patients, pharmacists should consider minimizing the use of drugs well-known to reason false-positive results, if possible. The an option of an suitable therapeutic agent for a patient relies on numerous factors, such together the effectiveness and adverse-effect file of the drug; therefore, minimizing the usage of medications displayed to reason false-positives must be weighed against clinical referee in product selection. However, for patients undergoing regular UDS testing, choosing an agent the very least likely to cause false-positives would be an essential consideration to aid minimize adverse results to patients from perhaps misinterpreted results.

Antidepressants

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

Furthermore, almost all TCAs can cause false-positive UDS results. Amitriptyline, desipramine, doxepin, and imipramine have actually been reported to cause false-positive results for LSD,3 and desipramine and also doxepin have additionally been reported to cause false-positive results for amphetamines.1,2 While hardly ever used, the monoamine oxidase inhibitor (MAOI) selegiline may also cause false-positive amphetamine results as result of its l-amphetamine and l-methamphetamine metabolites.2,4

Minimizing the usage of this agents in high-risk patient when possible may to decrease the risk of false-positive results. For patients inquiry an SSRI, pharmacologists should take into consideration using paroxetine, citalopram, or escitalopram and also minimizing the usage of fluoxetine and sertraline as soon as appropriate. When using an antidepressant come treat neuropathic pain, minimizing the usage of venlafaxine and TCAs and instead using duloxetine should be considered. Gabapentin and pregabalin have actually a minimal danger of causing false-positives and also are other options that might be used. Trazodone is an antidepressant generally used as a sleep aid. Minimizing that is use and instead making use of mirtazapine or sedative-hypnotics when suitable would be an additional consideration.1-4

Antipsychotics

In addition to antidepressants, plenty of antipsychotic agents have additionally been reported to cause false-positive results. Antipsychotics might be provided to act a range of psychiatric disorders, v the second-generation antipsychotics (SGAs) used more frequently as result of their an ext favorable side-effect profile contrasted to the first-generation antipsychotics (FGAs). The the SGAs, risperidone has actually been reported to reason false-positive LSD results;3,9 quetiapine, false-positive methadone and TCA results, which room attributed come quetiapine’s same in structure to methadone and TCAs.2-4 Two case reports of accidental aripiprazole gulp down in pediatric patients brought about false-positive amphetamine results.10 even if it is false-positives with aripiprazole may likewise occur in adult is uncertain.10 The FGAs chlorpromazine, prochlorperazine, haloperidol, and also thioridazine may all reason false-positive LSD results.3 Thioridazine may additionally cause false-positive amphetamine, methadone, and PCP results, and chlorpromazine cause false-positive amphetamine (due to similarities in structure) and also methadone results.1-4

When choosing an antipsychotic agent for high-risk patients, factor to consider should be provided to making use of lurasidone, olanzapine, or ziprasidone when appropriate. Aripiprazole may likewise be a reasonable option in adults, together no reports have uncovered false-positive outcomes in this population. However, pharmacologists should very closely consider the opportunity of a positive result being false should one occur with a patient on aripiprazole. Plenty of of the FGAs cause false-positive UDS results and also have a less favorable side-effect profile compared to the SGAs; thus, minimizing use of these agents when possible would be suggested.1-4

Other central Nervous system (CNS) Medications

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

Antiemetics

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

Antibiotics

Most antibiotics have actually not been indicated to cause false-positives with UDS immunoassays; however, quinolones and rifampin have actually been documented in small studies.4 all quinolones have actually the potential to reason a false-positive opiate screening result, with levofloxacin and ofloxacin having the highest possible risk. Ciprofloxacin, moxifloxacin, and norfloxacin showed cross-reactivity to opiates because of similar molecular structures, but at reduced levels than many immunoassay thresholds. Thus, this agents may be 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 been displayed to cause false-positives because that opioids, and also elimination calculations calculation a feasible false-positive an outcome for much more than 18 hours after a single oral sheep of rifampin 600 mg.13

OTCs

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

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

Nonsteroidal anti-inflammatory drugs (NSAIDs) have likewise been displayed to communicate with UDS immunoassays. Both ibuprofen and also naproxen have been documented to reason false-positive barbiturate4 and also 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 also opioid levels because of its metabolite’s similarity come the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have displayed false-positive amphetamine level due to comparable structures.1,2 To protect against misinterpretations, consider limiting these medications in high-risk populations.

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

Herbals

Herbal commodities may also interfere through UDS immunoassays. As morphine and also codeine are derived from opium poppy seeds, the input of reasonably small amounts of poppy seeds may an outcome in false-positives for opiates, including the intake of poppy-seed cookies (having ~1 tsp the poppy-seed filling) or poppy-seed bagels.2 Additionally, the sloop down of foodstuffs containing hemp, such as hemp-seed oil, have resulted in hopeful marijuana UDS results,2 and ephedra-containing commodities may reason false-positive methamphetamine results.17

Other natural supplements might be much less likely to reason false-positive test results. A examine of gingko biloba, observed palmetto, St. John’s wort, ginseng, garlic, eco-friendly tea, valerian, and cranberry did not 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 commodities can help minimize misinterpretation that UDS results.

Conclusion

By recognizing usual causes and medication involves for false-negatives and false-positives in UDS testing, pharmacists can improve care and administer insight into different medications because that patients. In every cases, clinical judgment should be used in choosing an proper therapeutic agent. Unexpected results from a UDS immunoassay should be checked with a confirmatory GC-MS or HPLC test. By to reduce medication-related reasons of false-positives and false-negatives, pharmacists have the right to potentially to decrease the need for added testing and also the negative consequences the misinterpreted pee immunoassay testing, hence optimizing patience care.

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REFERENCES

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