Gayle N. Scott, PharmD

DISCLOSURES June 18, 2019

Lab tests play a key role in clinical decision-making. More than 4000 lab testsare available, and an estimated 70% of clinical decisions are based on their results. Correct interpretation is critical.

The pharmacologic effects of drugs can change the results of lab tests; for example, levothyroxine increases thyroid levels, or lisinopril may increase potassium levels. But these changes do not involve interference with the labtest; that is, the result is accurate. True drug-lab test interactions are the result of a drug altering the test specimen, or direct interference from the drug itself reacting with the test reagents.^[1]

Despite their importance, surprisingly little is known about drug interactions with lab tests. Most information has been published as case reports about specific drugs. The US Food and Drug Administration (FDA) requires that drug-lab test interactions be described in the Warnings and Precautions section of the prescribing information; however, there are no industry requirements for drug-lab test interactions during drug development.

A review of the prescribing information for 10 commonly used prescription medications shows that eight made no mention of interactions with lab tests, one specifically stated “none known,” and one described an interaction (Table).

Table. Drug-Lab Test Interactions Listed in Prescribing Information for 10 Commonly Used Prescription Medications

Drug	Drug-Lab Test Interactions Listed
Albuterol inhaler	No
Amlodipine	None known
Atorvastatin	No
Levothyroxine	No
Lisinopril	No
Losartan	No
Metformin	No
Metoprolol	No
Omeprazole	Yes
Simvastatin	No

A recent view of the prescribing information for 1368 prescription drugs found that 134 (9.8%) included information about a specific lab test interaction, 31 (2.3%) stated that the drug did not interfere with lab tests, and four stated that there was no available information.^[1]

Lab tests that rely on immunoassay can be skewed by interfering antibodies, causing potentially misleading results at a rate of 0.4%-4%.^[2] For example, spironolactone may interfere with some immunoassays for serum digoxin measurement.^[3]

The most common examples of drug-lab test interactions are with urine specimens, because drugs may interfere with the assays for the chemical components in urine. For example, cephalosporins may alter urine glucose and ketone tests. Such products as Clinitest rely on reducing substances in urine to convert cupric sulfate to cuprous oxide, causing color changes depending on the amount of reducing substances present. Some cephalosporins can also reduce copper and cause false-positive results, leading to infrequent clinical use of copper reduction tests today with the development of more specific testing methods.^[1]

Urine screening for illicit drug use, which relies on immunoassay screening, is hampered by both unintentional and deliberate drug-lab test interactions. Interacting drugs can cause false-positive and false-negative results. For example, labetalol and ranitidine can cause a false-positive result for amphetamines, and rifampin can cause a false-positive result for opioids. False-positive results usually undergo more sensitive and specific testing.^[4]

Antibacterial agents are the drug class most frequently implicated in drug-labtest interactions.^[1] For example, daptomycin and telavancin can falsely prolong or elevate prothrombin time and the international normalized ratio. Daptomycin interacts with the recombinant prothrombin reagent, and telavancin interacts with phospholipid surfaces of the testing materials and interferes with the ability of the coagulation complexes to assemble for measurement.^[5,6]

Psychotropic drugs and contrast media are also reported to be frequent causes of drug-lab test interactions.^[1]

Even less information about lab test interference is available for over-the-counter drugs and herbal products, which have less detailed labelling requirements.

For example, the fact that acetaminophen can interfere with some continuous glucose monitors (CGMs) (particularly older versions) and cause falsely high glucose readings—a potentially serious interaction—does not appear on the package labelling for acetaminophen. CGMs monitor glucose in the interstitial fluid and convert this reading to a blood glucose level. CGMs measure glucose by converting glucose into an electronic signal, using glucose oxidase, which converts glucose to hydrogen peroxide. The hydroxyl group on acetaminophen is also oxidized at the CGM electrode, causing an error.

Other drugs, including lisinopril, albuterol, and atenolol, as well as red wine, have also been reported to cause falsely high CGM readings.^[7]

The herbal products Asian ginseng (Panax ginseng) and Siberian ginseng(Eleutherococcus senticosus) have been reported to interfere with some digoxin assays.^[8]

Clinical Takeaways

Because drug-lab test interactions may occur more frequently than currently recognized,^[1,9] what can clinicians do?

First, be wary. Because the FDA does not require drug-lab test interactions during new drug development, the absence of a drug-lab test interaction in the prescribing information does not preclude the existence of a yet-unreported interaction. In the case of over-the-counter and herbal medicines, even known interactions may not appear on package labelling. A complete list of all medications the patient is receiving or has recently received is essential in anticipating a potential drug-lab test interaction.

Second, remain vigilant. For test results that do not correspond with the clinical picture, clinicians and laboratory staff should obtain confirmatory testsby an alternate assay method if available.

Finally, investigations into many of the known drug-lab test interactions are a result of case reports. Publication of confirmed or suspected drug-lab test interactions can improve this understudied facet of healthcare. Reporting interactions to the FDA through MedWatch is also recommended.