Can Hydroxyzine Cause A False Positive For A Benzo?

In our latest question and answer, the pharmacist discusses whether or not hydroxyzine can cause a false-positive for benzodiazepines.

Question

Will a positive result occur on a 10 point urine drug test as a benzodiazepine if you are taking hydroxyzine?

Asked by cindy On Feb 14, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Feb 17, 2019
Hand Holding Urine Test

The question of whether or not a particular drug or supplement can cause a false-positive on a urine drug screening is a common one and a good one to ask.

The most commonly utilized tests are urine-based immunoassays, and they are subject to false positives. Studies that evaluate drugs associated with producing false positive results often provide huge lists. For example, the following have been reported to cause false-positive for opioids alone:

  • Delsym (Dextromethorphan)
  • Benadryl (Diphenhydramine)
  • Poppy seeds
  • Levaquin (levofloxacin)
  • Cipro (ciprofloxacin)
  • Verapamil

Immunoassay urine screenings are subject to false positive based merely on how the tests work:

  • Antibodies are used to bind to and react with a specified compound (such as a benzodiazepine).
  • When an antibody finds the compound it is looking for and binds to it; it produces a reaction. Such reactions are recorded as a 'positive' result.
  • Unfortunately, there is a problem with 'cross-reactivity'. Drugs that are not being tested for can occasionally react with the wrong antibody (i.e. 'cross-react'), resulting in a 'false positive.'

As you are concerned with hydroxyzine, let's take a look at that drug and see if it is associated with producing false-positive on drug tests.

What Is Hydroxyzine?

Hydroxyzine Molecular Structure

Hydroxyzine is a sedating first-generation antihistamine, structurally related to meclizine.

It has very similar effects to Benadryl (diphenhydramine), another first-generation antihistamine, but they are technically in different medication classes (hydroxyzine is a 'piperazine' antihistamine while Benadryl is an 'ethanolamine' antihistamine).

Hydroxyzine HCL Vs. Hydroxyzine Pamoate

Hydroxyzine is available as two different salt forms:

  • Atarax (hydroxyzine HCl)
  • Vistaril (hydroxyzine pamoate)

There is quite a bit of dispute regarding the different effects each salt form has. It is commonly thought that Atarax is used more for itching and Vistaril is used for anxiety and as a sedative.

While a particular individual may have slightly different effects with one or the other, most sources, including the prescribing information for both drugs, state they have near identical pharmacokinetic profiles.

The onset of effect for both is about 15 to 60 minutes after taking a dose, and both last around 4 to 6 hours. Hydroxyzine pamoate may cause slightly more sedation, however.

Does Hydroxyzine Cause False Positives For Benzodiazepines On Drug Tests?

Rx Bottle On Drug Test Form

Benzodiazepines are among the most commonly prescribed drugs and are used for a wide variety of indications, including anxiety disorders, insomnia and as a muscle relaxant.

Drugs in the benzodiazepine class include:

  • Alprazolam
  • Chlordiazepoxide
  • Clonazepam
  • Diazepam
  • Lorazepam
  • Midazolam
  • Temazepam
  • Triazolam

While useful, benzodiazepines can cause physiological dependence and have a risk of abuse and misuse. Therefore, they are often included in drug screening tests.

Although there are reports of several drugs causing false-positives for benzodiazepines on drug tests (e.g., sertraline, oxaprozin), Hydroxyzine has not been associated with it. If you tested positive for a benzodiazepine recently on a urine-based drug test, hydroxyzine likely was not the culprit.

Nevertheless, hydroxyzine has been reported to cause a false positive for another class of drugs, tricyclic antidepressants, or TCAs.

One of the most commonly cited studies on urine drug screening, 'Urine Drug Screening: Practical Guide for Clinicians ', states the following regarding TCA false-positives:

Antihistamine agents (eg, cyproheptadine, carbamazepine, cyclobenzaprine, and quetiapine) have often been reported to interfere with the serum immunoassay for TCAs because of their 3-ringed structures. Although structurally dissimilar to TCAs, the antihistamines diphenhydramine, hydroxyzine, and cetirizine (hydroxyzine's metabolite) have also been shown to interfere with serum TCA immunoassay in overdose situations. Unfortunately, these case reports did not test for interference in the urine immunoassay, except for quetiapine and cyclobenzaprine.

It is important to note in the above passage, that even though hydroxyzine is associated with false-positives for tricyclic antidepressants, case reports have not seen it occur on urine tests, but rather only in serum blood tests.

How Long Does Hydroxyzine Stay In The Urine?

Regarding long hydroxyzine stays in the urine, that will vary by the individual. For most, it will be detectable for 3 to 5 days.

Hydroxyzine has a half-life between 14 and 25 hours. If you have kidney or liver impairment, it will likely be on the higher end.

It generally takes 4 to 5 half-lives for a drug to be considered completely metabolized and eliminated for the body. Therefore, based on the half-life of 14-25 hours, that translates to roughly 3-5 days.

Will Hydroxyzine Show Up On A Hair Follicle Test?

Hydroxyzine can be seen on hair follicle tests, but there have been no studies completed testing how long it is detectable for. Most studies state as a general rule, hair follicle tests have the widest window of detection, between 7 and 100 days.

Studies that have tested for diphenhydramine, a similar antihistamine, show that it is detectable for at least 40 days, and likely up to 100 days.

What To Do If A False-Positive Occurs

If you received a positive result on a urine drug test that you think is an error, you should request more specific testing that does not rely on antibodies. The most common type of non-antibody test is gas chromatography with mass spectrometry.

This test can identify specific drug compounds in a sample and does not rely on antibody reactions, and therefore, 'cross-reactivity' is not an issue.

References
  • Elsevier ClinicalKey: Hydroxyzine Monograph (Accessed 2/13/19)
  • False-positive serum tricyclic antidepressant concentrations using fluorescence polarization immunoassay due to the presence of hydroxyzine and cetirizine. PubMed
  • Urine drug screening: Practical guide for clinicians. Semantic Scholar
  • Clinical Interpretation of Urine Drug Tests: What Clinicians Need to Know About Urine Drug Screens. Mayo Clinic Proceedings
  • Commonly prescribed medications and potential false-positive urine drug screens. PubMed
  • Hair analysis for diphenhydramine after surreptitious administration to a child. PubMed
  • A Review of Drug Detection Testing and an Examination of Urine, Hair, Saliva and Sweat. National Drug and Alcohol Research Centre

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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