‘Prescribe ivermectin for COVID-19 only in large-scale randomized trials’

Ivermectin is a drug approved by the United States Food and Drug Administration (FDA) to treat parasites in animals and in humans with intestinal strongyloidiasis (roundworm) and onchocerciasis (river blindness) orally, as well as ectoparasites and skin conditions topically.  Ivermectin is not approved by the FDA to treat or prevent COVID-19.

Nonetheless, prescriptions of ivermectin by U.S. health care providers increased more than tenfold from 3,589 per week pre-COVID-19 to 39,102. In addition, the U.S. National Institutes of Health (NIH), World Health Organization (WHO) and European Medicine Agency (EMA) have all advised against using ivermectin to treat or prevent COVID-19.     

In a commentary published in the journal Therapeutic Innovation & Regulatory Science, researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators, urge all health care providers to always prioritize compassion with reliable evidence on efficacy and safety. As such, they recommend a moratorium on prescribing ivermectin to treat or prevent COVID-19, except to provide the necessary evidence in data from large-scale randomized trials.

“The evidence to support ivermectin to treat or prevent COVID-19 includes some basic research and inconsistent clinical observations that contribute to the formulation of a hypothesis of efficacy in COVID-19,” said Scott M. Alter, M.D., M.B.A., co-author, associate research professor and an associate professor of emergency medicine, FAU Schmidt College of Medicine. “Currently, data from peer-reviewed published randomized trials of sufficient size, dose and duration are sparse to reliably test the hypothesis of small-to-moderate benefits on clinically relevant endpoints.”

The researchers caution ivermectin is not a benign drug and has reported side effects that include cutaneous, gastrointestinal and cardiovascular symptoms. Specifically, skin rash, nausea, vomiting, diarrhea, stomach pain, hypotension, dizziness, and seizures have been reported.

“For ivermectin in treatment or prevention of COVID-19, health care providers should reassure all patients that if sufficient evidence were to emerge, then this drug would be considered a therapeutic innovation and regulatory authorities would approve the drug,” said Lisa Clayton, D.O., co-author, associate professor and chair, Department of Emergency Medicine, FAU Schmidt College of Medicine.

The authors note that last year, Merck, the manufacturer of ivermectin, stated that they also believe that the available data do not support the safety and efficacy of the drug beyond the doses and populations indicated in the regulatory agency-approved prescribing information. In addition, last summer, a meta-analysis of 14 trials, concluded that the currently available evidence does not support the prescription of ivermectin for treatment or prevention of COVID-19.

“Doing more good than harm in COVID-19 requires concerted efforts by competent and compassionate health care providers, who are justifiably the most trusted, to communicate with their patients the therapeutic and preventive measures of proven benefit,” said Charles H. Hennekens, M.D., Dr.PH, senior author, first Sir Richard Doll Professor and senior academic advisor, FAU Schmidt College of Medicine. “Most importantly, health care providers must remain cognizant that achieving much higher vaccination rates is essential to prevent, mitigate and control the pandemic, especially in the U.S.”  

Hennekens added, “Among the seven richest countries with a population greater than 10 million, the U.S. has the lowest vaccination rates and highest COVID-19 death rates.”

The authors also say that Americans should be aware that with respect to therapeutic innovations, there is a process for drug development for a specific indication and for that application to receive permission to market the therapeutic or drug for other diseases. In addition, for regulatory science, there is an orderly and unbiased process to achieve regulatory approval.

As a cautionary note, the researchers compare similarities in prescriptions of ivermectin to hydroxychloroquine, whose emergency use authorization was withdrawn by the FDA following the results of large-scale trials that demonstrated a lack of efficacy and possible harm for the treatment and prevention of COVID-19.

“At present, there are remarkably efficacious and safe preventive measures, especially vaccinations as well as several therapeutic innovations of proven benefit,” said Hennekens. “It would be unfortunate and create avoidable morbidity and mortality if health care providers were to prescribe a drug of unproven benefit and safety for COVID-19, such as ivermectin, to patients as an alternative to therapeutic innovations of proven benefit in treatment or, even more importantly, vaccinations to prevent COVID-19.” 

Other co-authors are first author Andrea Molnar, M.D., clinical assistant to Nicolas R. Breuer, M.D., affiliate assistant professor, FAU Schmidt College of Medicine; Stephanie Lau, M.D., and Maja Berges, LIV Plastic Surgery; Raymond B. Masa, A.D.N., an intensive care unit (ICU) nurse at Boca Raton Regional Hospital, part of Baptist Health; Joshua J. Solano, M.D., assistant professor; and Richard D. Shih, M.D., professor of emergency medicine, both in FAU’s Department of Emergency Medicine; as well as David L. DeMets, Ph.D., Emeritus Halperin Professor and founding chair of the Department of Biostatistics and Informatics; and Dennis G. Maki, M.D., Ovid O. Meyer Professor of Medicine, and director of the COVID-19 ICU, both at the University of Wisconsin School of Medicine and Public Health.  

Hennekens and Maki have been collaborators since 1969, when they served as lieutenant commanders in the U.S. Public Health Service as epidemic intelligence service (EIS) officers with the U.S. Centers for Disease Control and Prevention. They trained under Alexander D. Langmuir, M.D., founding director of the EIS and Donald A. Henderson, M.D., director of virology. Langmuir and Henderson played crucial leadership roles in collaboration with local, state, national, and international public health authorities in the mitigation and containment as well as eradication of polio and smallpox.

- FAU -

About the Charles E. Schmidt College of Medicine:

FAU’s Charles E. Schmidt College of Medicine is one of approximately 155 accredited medical schools in the U.S. The college was launched in 2010, when the Florida Board of Governors made a landmark decision authorizing FAU to award the M.D. degree. After receiving approval from the Florida legislature and the governor, it became the 134th allopathic medical school in North America. With more than 70 full and part-time faculty and more than 1,300 affiliate faculty, the college matriculates 64 medical students each year and has been nationally recognized for its innovative curriculum. To further FAU’s commitment to increase much needed medical residency positions in Palm Beach County and to ensure that the region will continue to have an adequate and well-trained physician workforce, the FAU Charles E. Schmidt College of Medicine Consortium for Graduate Medical Education (GME) was formed in fall 2011 with five leading hospitals in Palm Beach County. The Consortium currently has five Accreditation Council for Graduate Medical Education (ACGME) accredited residencies including internal medicine, surgery, emergency medicine, psychiatry, and neurology.

About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.