COVID-19 Warnings: Usage Of Antiviral Of Lopinavir-Ritonavir To Treat COVID-19 Linked To Numerous Drug Interactions And Even Deaths
: Researchers from COVID-19 Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen de Valme- Spain have discovered that the usage of the antivirals Lopinavir-Ritonavir (LPV-r ) can lead to numerous drug interactions that can be detrimental to health conditions and even cause death in certain situations as a result of these interactions.
Despite numerous studies that have shown that the drug has no efficacy against the SARS-CoV-2 coronavirus (https://www.thailandmedical.news/news/covid-19-drugs-recovery-trial-study-confirms-lopinavir-ritonavir-has-no-clinical-benefits-in-hospitalized-covid-19-patients
), there are still many third world countries still using Lopinavir-Ritonavir to try to treat COVID-19. Thailand hilariously even had some of its doctors and officials publicly claiming that they had invented a treatment protocol to treat COVID-19 using Lopinavir-Ritonavir and Oseltamivir and that the studies would be published in a medical journal. That study never materialized (maybe because they could not write English!) and no action was ever taken against the doctors, the officials and the non-credible media that covered the story on grounds of spreading fake news and misinformation. (Thailand latest claim is that they have an effective COVID-19 vaccine on the way. Just a few years ago there also were claims also by Thailand to finding a cure for Ebola and also a vaccine for HIV!)
What is more concerning is that the already hepatoxic drug is now known to be having drug-drug interactions (DDI,) affecting a wide variety of commonly used medications.
Among those, lipid lowering drugs, antiarrhythmics, cardiovascular drugs, analgesics or anticoagulants are frequently used by aged patients. These older patients are more likely to present with more severe COVID-19 requiring admission and respiratory support, and, due to this, more likely candidates to receive drugs with potential antivirals against such as Lopinavir-Ritonavir (LPV-r).
It was observed that management of LPV-r by noninfectious diseases doctors, not used to the DDI profile of this drug, along with the need for a fast response and the overwhelming burden of COVID-19 in some areas might have led to a high rate of major DDI between LPV-r and concomitant prescriptions. DDI could have an impact on the tolerability of LPV-r and DDI may even be associated with worse outcomes.
The study involved Four hundred and sixty-nine patients who had a confirmed diagnosis of SARS-CoV-2 infection during the study period.
Among them, 125 (27%) individuals were prescribed LPV-r for COVID-19. The median (Q1-Q3) duration of LPV-r treatment was 5 (3-7) days, ranging from 1 to 14 days.
Overall, LPV-r had DDI with concomitant medications in 103 (82%, 95% CI: 75%-89%) subjects. In 97 (78%, 95% CI: 69%-85%) patients, potential DDI were disclosed, and in 33 (26%, 95% CI: 19%-35%) individuals major DDI were found.
LPV-r was discontinued due to side effects in 31 (25%) patients. One patient with preexisting chronic end-stage renal failure suffered grade 3 diarrhea. LPV-r was discontinued, but renal failure worsened, and the patient ultimately died. Another p
atient with cardiovascular disease was treated with amiodarone for cardiac arrhythmia. He presented an orthostatic syncope, and LPV-r was discontinued, but he died of sudden death afterwards.
Co-administration of LPV-r with drugs that are major substrates of and highly dependent on CYP3A for clearance is associated with increased plasma concentrations of such drugs or their metabolites. In the study, many commonly used medications with that metabolic interaction with LPV-r were prescribed to patients with COVID-19. Antiarrhythmics, symvastatin or budesonide were found to be administered to the study patients. Elevated plasma concentrations of some of those medications are associated with life-threatening reactions. In this regard, the researchers found a significantly higher frequency of deaths among patients who were treated with medications with major DDI with LPV-r.
However, after adjustment in a multivariate model, drugs with major DDI with LPV-r were not independently associated with the risk of death. Instead, the main predictor of death was the Charlson index. Therefore, the patient profile, i.e. older individuals with concomitant diseases needing drugs posing contraindications with LPV-r, accounted for the association between deaths and major interactions with LPV-r.
The study findings are published on a preprint server and are currently being peer-reviewed. https://www.medrxiv.org/content/10.1101/2020.07.30.20165027v1
Perhaps in countries where the drug was used and deaths had occurred, the relatives of the deceased should start initiating investigations, and also criminal and civil proceedings against the doctors and health officials who advocated using these drugs to treat COVID-19 despite having no prior proof . It would also be interesting to see how many patients actually died as a result of these drugs and not COVID-19.Such studies should also be extended cover other drugs that were being used despite no efficacy including chloroquine, hydroxychloroquine and favipiravir(avigan)
For more COVID-19 Warnings
, keep on logging to Thailand Medical News.