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Clinicians prescribed hydroxychloroquine (HCQ) and ivermectin inappropriately to thousands of children with acute COVID-19, according to a retrospective cohort study.

In a large U.S. all-payer database, 3,602 ivermectin prescriptions and 813 HCQ prescriptions for kids with acute COVID were identified after guidelines recommended against their use, though prescription rates for these medications were less than 1% -- 0.03% for HCQ and 0.14% for ivermectin, reported Julianne Burns, MD, MSCE, of Stanford University in California, and colleagues in .

"Although this proportion may seem reassuringly low, the overall incidence of COVID-19 translates into ineffective and potentially harmful prescriptions for many children," the authors noted. However, it is somewhat reassuring that there were no medical claims for related adverse drug reactions within 28 days of the prescriptions, they added.

"Low mortality and hospitalization rates in our cohort suggest these infections were less likely to be serious, further underscoring the risks of an unnecessary prescription against any perceived benefits," they wrote.

By September 2020, endorsed by the Pediatric Infectious Diseases Society recommended against HCQ for COVID outside of a clinical trial. In February 2021, the Infectious Diseases Society of America published against the use of ivermectin outside of a trial. The organization recommended against ivermectin use for COVID altogether by July 2022.

Notably, there was substantial variation in prescribing rates among states. Arkansas had the highest HCQ prescription rate, at 0.13% during the study period, and Oklahoma had the highest ivermectin prescription rate at 0.56% -- both about four times the national average.

Prescribing rates for HCQ peaked in April 2020, and for ivermectin in July-August 2021. Notably, at the peak of ivermectin prescribing, its prescription rate was 1.6% in three states -- Oklahoma, Texas, and Arkansas. At that time, Oklahoma alone had an ivermectin prescription rate of 1.9% -- 13.6 times the national average, Burns and team pointed out.

Teenagers were far more likely to be prescribed HCQ or ivermectin than younger children (P<0.001 for both), as were children with commercial insurance versus those with public insurance (P<0.001). In addition, children living in rural regions had about 3.5 times the odds of being prescribed ivermectin compared with those in urban areas (P<0.001), while kids whose families had lower median household incomes had about two times the odds of receiving ivermectin versus those with higher household incomes (P=0.003).

Among prescribers, general practitioners had prescribing rates of hydroxychloroquine and ivermectin that were 15 and 8 times the rate of pediatricians.

"Relatively few clinicians were responsible for large numbers of prescriptions, echoing the 'pill mills' where individual clinicians have written tens of thousands of HCQ and ivermectin prescriptions through large telehealth operations," Burns and colleagues wrote. However, inpatient prescribing of non-recommended medications was low, "suggesting guidelines were more likely to be followed in hospitalized patients."

Although COVID cases increased in 2022, prescriptions for non-recommended medications began to wane -- perhaps due to more mild illness, targeted messaging, and the retraction of studies about ivermectin effectiveness, the authors posited.

For this study, Burns and colleagues analyzed data from the Komodo Healthcare Map, a large all-payer claims database representing 330 million patients in the U.S. They identified over 3 million pediatric COVID-19 diagnoses from March 2020 through December 2022.

COVID diagnoses that occurred before the publication of pediatric guidelines advising against the use of HCQ or ivermectin were excluded from the study. After exclusion, there were 2,885,994 diagnoses included in the HCQ analysis and 2,555,469 diagnoses included in the ivermectin analysis.

Among non-recommended medications prescribed for COVID, the researchers found that only HCQ and ivermectin had prescription rates that met the prespecified prescribing rate criteria of >0.01%.

The authors noted that one limitation to the study was that HCQ or ivermectin obtained from sources such as veterinary practices or prescriptions from family members were not included in their analysis.

Correction: This article previously stated that kids from rural areas whose families had lower median household incomes had higher odds of receiving ivermectin versus those with higher household income. This has been changed to reflect that this applies to all the kids, not just kids from rural areas.

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