Can Phrenilin (Acetaminophen; Butalbital) Cause A Positive Drug Test For Amphetamine?

Phrenilin, which contains butalbital, has not been reported to cause false-positives for amphetamine on drug screenings. The pharmacist discusses this and more.


Will the prescription of phrenalin show up in a drug test as an amphetamine?

Asked by KIT On Mar 11, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Mar 12, 2019
Man Holding Urine Cup With Title Phrenilin Drug Test For Amphetamine

Phrenilin is a prescription product that contains two active ingredients:

  • Acetaminophen
  • Butalbital

Butalbital is classified as a 'barbiturate' and is often used in combination with analgesics (like acetaminophen) for its sedative and muscle relaxant properties.

Although barbiturates aren't generally included on standard 5-panel urine drug screenings (amphetamines, cocaine, marijuana, opiates and phencyclidine (PCP) are standard), there certainly are tests that can identify them since they are drugs that can be abused and have a fairly strong potential for addition.

Phrenilin Causing False-Positives On Drug Tests?

There isn't any data to indicate that barbituates (such as butalbital, which is contained in Phrenilin) are associated with causing false-positives for other classes of drugs, like amphetamines.

However, there is significant evidence to suggest that NSAIDs, like ibuprofen and naproxen, can cause 'false-positive' results for barbiturates.

NSAIDs Causing False-Positives For Barbituates

One of the largest review studies on the matter of substances causing false-positives on urine drug-screenings, published in the American Journal of Health-System Pharmacy, specifically lists NSAIDs as known compounds causing false-positives for barbituates.

Another study, published in the Journal of Family Practice, estimates that NSAIDs cause false-positives on urine drug screenings around 0.4% of the time.

The two most commonly reported NSAIDs responsible for false-positives are:

  • Naproxen (brand names Aleve, Anaprox)
  • Ibuprofen (brand names Advil, Motrin)

Phenytoin has also been reported to cause false-positive readings.

False-Positives For Amphetamines

As mentioned, barbituates like Phrenilin have not been associated with causing false-positives for amphetamines. Numerous other drugs have, however.

All of the following have been reported in studies to have caused false-positive urine screenings for amphetamines:

  • Amantadine
  • Brompheniramine (Dimetapp)
  • Bupropion (Wellbutrin)
  • Chlorpromazine
  • Chloroquine
  • Desipramine
  • Doxepin
  • Labetalol
  • Methylphenidate
  • Phenylephrine (Sudafed PE)
  • Promethazine (Compazine)
  • Pseudoephedrine (Sudafed)
  • Ranitidine (Zantac)
  • Selegiline
  • Thioridazine
  • Trazodone
  • Trimethobenzamide
  • Venlafaxine (Effexor)
  • Vicks inhaler

Why Do False-Positives Happen?

False Positive In Red Text

The rate at which false-positive drug tests occur isn't exactly known, since most of the time, secondary testing to confirm a positive result isn't done.

Nevertheless, some studies suggest that urine-based immunoassay drug tests (the most common type of initial screening) can be highly inaccurate. Estimates of the rate of false-positives range as high as 20%!

False-positives aren't the only problem either. False-negatives (testing negative for a drug you are taking) happen often as well. This can have serious consequences, especially if you are being tested by your doctor to ensure you are taking a prescribed therapy (e.g. at a pain clinic).

The problem is with the type of test that is used on urine screenings. They are generally immunoassay tests, which rely on an antibody to bind to and react with a specific drug substance (like a barbiturate) in a sample. Sometimes though, the antibody will bind to the wrong substance, and produce a reaction (a 'false-positive').

The high rate of false-positives is why most studies reviewing the matter suggest that urine-based immunoassay screenings should be just that, an initial screening, and not relied on for a definitive result.

To get a definitive result (or to rule out a potentially inaccurate reading), there are more specific tests, notably gas chromatography-mass spectrometry, which can identify specific compounds in a sample, and don't rely on antibody reactions. These tests just aren't used first-line due to their expense and the time involved.

One study sums up why urine tests should only be used as a screening tool:

"With the increased availability of onsite drug testing and the variety of products associated with reports of false-positive results in the literature, confirmation of results is needed. Failure to follow up to determine if a false positive may have occurred could result in unnecessary adverse consequences for the patient (e.g., incarceration, employment denial, loss of privileges)."


  • Phrenilin, a prescription medication containing butalbital, has not been reported to cause false-positives for amphetamines on urine drug screenings.
  • Several other drugs have been reported to cause amphetamine false-positives, including Zantac (ranitidine) and Sudafed (pseudoephedrine).
  • Naproxen and ibuprofen have been associated with causing false-positives for barbituates like butalbital.

  • Elsevier ClinicalKey: Phrenilin Monograph
  • Commonly prescribed medications and potential false-positive urine drug screens. PubMed
  • Pharmacological Treatment of Insomnia. PubMed
  • Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques. PubMed
  • One Hundred False-Positive Amphetamine Specimens Characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry. PubMed
  • False-positive barbiturate test in urine owing to phenytoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin. PubMed
  • Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. PubMed
  • Commonly prescribed medications and potential false-positive urine drug screens. PubMed

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of 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! Office: 716-389-3076

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