Friday, December 20, 2019 Show Our series on interpreting unexpected results concludes with a discussion on the interpretation of benzodiazepine results from Aegis Sciences Corporation. Please note that the interpretation of benzodiazepine results differs when using presumptive vs. definitive testing methods, and may differ among laboratories. The information provided here is intended to assist providers with deciphering benzodiazepine results from Aegis, which have undergone definitive testing by liquid chromatography/tandem mass spectrometry prior to reporting as positive. Considerations for Interpreting Unexpected Results In the case of unexpected positive benzodiazepine results, consider the following drug exposures:
Alprazolam (Xanax®): Metabolizes to alpha-hydroxyalprazolam; reported as Alprazolam A patient taking alprazolam, clonazepam, flurazepam, or lorazepam will not test positive for benzodiazepine metabolites on an Aegis report. Opportunities for Exposure Prescription: Benzodiazepines are controlled substances, and legitimate prescriptions would show up on the prescription drug monitoring program (PDMP) in most cases. Please note that chlordiazepoxide, when administered with clidinium (Librax®), is not a controlled substance in many jurisdictions and may not show up on the PDMP in these states. Procedural Administration: Abenzodiazepine may be administered as an anxiolytic or sedative prior to medical procedures. If the medication was directly administered to the patient by the treating provider, record of this may not be part of the patient’s PDMP report. A review of medical records may be necessary to determine the medications given to the patient prior to or during a procedure. Hospitalization/Emergency Department Visit: Patients who arrive at the emergency room with a suspected poisoning or overdose may be given benzodiazepines depending on their presenting symptoms and the source of the toxicity. A benzodiazepine may also be given as an anxiolytic, pre-procedurally, or for treatment of a seizure. If the patient reports a recent hospitalization or emergency department visit, follow-up with the hospital may be necessary to determine what medications were administered to the patient. Illicit Exposure: Sources of illicit exposure may include use of another person’s prescription drug, acquisition of counterfeit or other illicit drugs unknowingly laced with benzodiazepines, or exposure to illicitly manufactured benzodiazepines which may share metabolites with FDA-approved benzodiazepines.3 What medication is the patient prescribed? In many cases, the result interpretation may be clarified by correctly indicating the patient’s prescribed medications when ordering testing. Any questions about how to list medications as prescribed on an Aegis laboratory requisition may be directed to the Aegis Client Services department at 1-800-533-7052. In general, the following guidance may be helpful:
Does the patient have altered gastrointestinal (GI) function or recent GI illness? If evaluating urine results, is the sample dilute? Further information regarding specimen tampering is available in the Aegis Clinical Reference Guide at https://www.aegislabs.com/resources/clinical-reference-guide/. Click on the title “Specimen Validity Testing and Specimen Tampering” to download a copy of this chapter. Are there concerns with drug and sample stability such as improper storage or delays in shipment? If evaluating urine results, the sample pH may be an indicator of sample stability. Although the impact of urine pH would not likely be so significant to cause unexpected negative results, providers may consider that an elevated urine pH may be a natural physiologic response to regulate the body’s acid-base balance, or it may also be elevated if the urine was not stored properly prior to shipment. In the case of improper storage, drug degradation contributing to unexpected negative results may be possible. Clonazepam in particular is more prone to stability issues. Losses of 7-aminoclonazepam in urine averaging 43% have been reported under refrigerated conditions at 2 months.7 A 76% drop in clonazepam concentration has occurred in an oral fluid specimen stored at room temperature overnight.8 Complete loss of clonazepam in oral fluid has occurred in 7 days at room temperature.9 In oral fluid, losses of 7-aminoclonazepam up to 20% and 33% have been observed at room and refrigerated temperatures, respectively, over a week.10 Providers may consider these known issues particularly when evaluating unexpected negative clonazepam results. These stability issues along with as-needed dosing and/or low doses may further increase the likelihood of unexpected negative results. Further information regarding specimen stability is available in the Aegis Clinical Reference Guide at https://www.aegislabs.com/resources/clinical-reference-guide/. Click on the title “Drug Stability and Toxicology Testing” to download a copy of this chapter. Is the patient on dialysis? Point of Care Testing Considerations False negative immunoassay results may also occur due to failure of the assay to react to drug-specific markers such as alpha-OH-alprazolam, 7-aminoclonazepam, 2-hydroxyethylflurazepam, and lorazepam glucuronide.6,11,12,16,18-21 At Aegis, we understand your concerns as you evaluate definitive drug testing results. Unexpected benzodiazepine results may be indicative of noncompliance, drug misuse, or diversion, and we welcome your calls and e-mails for assistance in interpreting these results. NOTICE: The information above is intended as a resource for health care providers. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct. DOWNLOAD CLINICAL UPDATE References: 1. Baselt, RC. Disposition of toxic drugs and chemicals in man. 11th ed. Seal Beach, CA: Biomedical Publications; 2017. What can show up as benzodiazepine in a urine test?Some other medicines can cause a false positive result in benzodiazepine urine tests.. Tolmetin.. Naproxen.. Etodolac.. Fenoprofen.. Oxaprozin.. Can antidepressants test positive for Benzos?Certain antidepressant drugs are more prone to false-positive readings. For example, Wellbutrin (bupropion), Prozac (fluoxetine), and Desyrel (trazodone) can all potentially show up as amphetamines in a drug screen. Similarly, Zoloft (sertraline) may show up as a benzodiazepine.
Can ibuprofen make you test positive for Benzos?Ibuprofen. This over-the-counter pain reliever can cause a drug test to show up as positive for barbiturates, benzodiazepines, and marijuana. 12000 mg of ibuprofen, it is thought, may interfere with the enzyme used in the testing method.
What is the most common falseFalse-positive results for amphetamine and methamphetamine were the most commonly reported. False-positive results for methadone, opioids, phencyclidine, barbiturates, cannabinoids, and benzodiazepines were also reported in patients taking commonly used medications.
What can cause a false negative for Benzos?One reason for false-negative clonazepam results is that the drug appears in the urine almost entirely as 7-aminoclonazepam, a metabolite that is not detected by many commercial immunoassay screens. A similar challenge exists for some other extensively metabolized benzodiazepines.
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