TOXICOLOGY
Medication Prescribing in Time of COVID, Unproven Remedies, Overstepped Autonomy, Known Harms: A Toxicologic Argument Against Ivermectin for COVID-19 Noah Berland, MD MS, Mehruba Anwar Parris, MD FAAEM
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t has always been attributed to Paracelsus the toxicologic axiom that the dose makes the poison, one of the main tenets of modern day medical toxicology. And today, toxicologists are more than familiar with the EBM world’s issues with a large proportion of toxicologic research and treatments, so it is us toxicologists that are possibly the most informed on the weaknesses to be aware of when trying to treat a disease process without good evidence. In toxicology the rea-
• There is no other alternative treatment and it is believed that the potential benefits outweigh the risks.
Treating patients with COVID-19 using ivermectin does not follow any of the above three points. This has been true for a number of months. At present there are three systematic reviews that we are aware of, 1) is a Cochrane Review1 showing no statistical benefit and clearly relates the clear uncertainty and poor quality of studies, 2) by Roman et al.2 also showing no benefit, noting the paucity and poor quality of evidence, and 3) Bryant et al.3with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. AREAS OF UNCERTAINTY: We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID19 infection. DATA SOURCES: We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion. Figure 1, Prescribing Patterns of Ivermectin from March 22, 2019 though August 13, 2021. https://emergency. THERAPEUTIC ADVANCES: Meta-analysis of cdc.gov/han/images/graph_449.png4 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.190.73; n = 2438; I2 = 49%; moderate-certainty evidence which includes many non-peer-reviewed studies, performs questionable statistical techniques, and includes the now retracted Elgazzar et al paper, showing possible statistical Figure 2, Google Trends Data comparing internet searches for Ivermectin (Blue) with Scabies (Red), significance, but even on rudimentary viewing normalized to a maximal scale of 100. https://trends.google.com/trends/explore?date=2019-08-06 2021-09-06&geo=US&q=ivermectin,scabies6 of the results, does not appear to hold up. Lawrence et al. summarized the inherent risks in relying on meta-analyses of poor-quality data best in their corresponsons to provide treatment recommendations that are not based on randence in Nature titled “The lesson of ivermectin: meta-analyses based domized controlled trials are the following: on summary data alone are inherently unreliable.” Yet, many physicians • The current treatment is well established with studies/case series that continue to prescribe ivermectin to their patients. Just as in the opioid overdose epidemic, we physicians are not blameless on promulgating demonstrate a benefit and it would be unethical to withhold the treatthis false hope, with prescriptions up from a pre-pandemic baseline of ment to perform a trial. • The overdose is lethal and withholding any treatment is likely to cause about five thousand a month, week to the week of August 13th of 88 thousand prescriptions, a 24-fold increase (Figure 1).4 The American death, and the mechanism of the treatment is biologically plausible.
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COMMON SENSE NOVEMBER/DECEMBER 2021
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