Hydroxyurea Interferes With CGM Readings in Diabetes

Miriam E. Tucker

May 18, 2021

The discovery that hydroxyurea interferes with the functioning of the Dexcom G6 continuous glucose monitor (CGM) in patients with diabetes came about from communication between one patient and one physician, setting an example for future similar situations.

Dexcom sent notices to clinicians and patients in February 2020 following the report of the case, and additional information was added to the Dexcom website a month later.

Hydroxyurea is an uncommonly used medication for treating certain cancers, sickle cell disease, and thrombocythemia.

"Hydroxyurea is a small electroactive molecule that can interact with our sensor," a Dexcom representative told Medscape Medical News. Acetaminophen (paracetamol) was already known to interfere with the Dexcom G5 but to a far lesser degree with the G6.

The case report that led to the revision of the device's label in early 2020 was published in the May 2021 issue of Diabetes Care by Emily D. Szmuilowicz, MD, of the Division of Endocrinology, Metabolism and Molecular Medicine at the Northwestern University Feinberg School of Medicine, Chicago, Illinois, and colleagues.

Szmuilowicz told Medscape Medical News: "I think this is...an important reminder of the small incidence of limitations that we all need to be aware of as clinicians…These types of interferences are so infrequent in comparison to the massive benefits we derive from CGM and hybrid closed-loop pumps" in patients with diabetes.  

Patient Reports Previously Unrecognized Problem, Doctor Follows Up

The patient was a 69-year-old woman with type 1 diabetes who used the Dexcom G5 and G6 systems, and who was also taking 1000 mg of hydroxyurea daily for essential thrombocytosis. She reported to Szmuilowicz, her endocrinologist, that her Dexcom sensor readings were always high after she took the medication, no matter the time of day, or whether she had eaten, and that they conflicted with fingerstick readings.

In subsequent testing with the patient wearing both the Dexcom G6 and a different CGM, the Abbott FreeStyle Libre, for 3 days, glucose readings were similar until the patient took hydroxyurea in the fasting state, at which point they diverged. For example, at one point the Dexcom read 254 mg/dL while the Libre showed 128 mg/dL. At another, the readings were 194 mg/dL versus 89 mg/dL, respectively. The Dexcom glucose readings, but not the Libre's, remained high for 6-10 hours following hydroxyurea administration.

The patient was not harmed, but had she been wearing a hybrid-closed loop system that relies on the CGM data to determine insulin dosing she may have experienced hypoglycemia and undue risk, Szmuilowicz and coauthors point out.

However, they write, "These accuracy limitations are not unique to any particular manufacturer or technological platform. The onus is upon clinicians to carefully evaluate individual scenarios in which any apparent incongruence exists."

Indeed, in March 2021 Medtronic also issued a statement about potential hydroxyurea interference with its CGM sensors, although the company had not received any reports of patient harm.  

And although the FreeStyle Libre appears not to have the problem with hydroxyurea, its website lists aspirin and ascorbic acid as potentially interfering substances.

Lessons Learned: Listen to Patients, Keep Eyes Open

The experience raises important issues, Szmuilowicz said.

For one, "Our patients are so intimately involved and know so much more about these individual glycemic patterns that we really need to listen when they notice these things...We're going to discover all kinds of things we don't already know and just because it doesn't exist in the medical literature is certainly not a reason to say it isn't true."

In addition, she pointed out that with the rapid embrace of remote monitoring and data interpretation, especially during the COVID-19 pandemic, "even though these are such wonderful advances that are so useful and convenient for so many reasons, there is still an important role for interpersonal communication between clinician and patients to talk about these patterns that patients see on an everyday basis that you would never be able to glean if you didn't speak to a person."

Finally, she observed, "None of these tests are going to be perfect. It's a reminder of why there's such an important human part of caring for patients, of keeping that dialog open and keeping our eyes open for anything that doesn't seem to fit the traditional paradigm. I think that's a key lesson that came from the story."

The work was supported by Northwestern University. Szmuilowicz has reported no relevant financial relationships. Aleppo has reported serving as a consultant for Dexcom and Insulet Corporation and has received research support from Dexcom, Eli Lilly, and Insulet Corporation.

Diabetes Care. 2021;44:e89-e90. Abstract

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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