Monash Australia research about Ivermectin in COVID was a huge story in 2020. The researchers reported that anti-parasitic drug, Ivermectin, eliminated SARS-CoV-2 in cells in 48 hour. The study was done in laboratorial experiments and the result was posted on April 3rd 2020. The university updated the news1 on August 17th 2021 and the main theme was that “Dr Wagstaff has been working to establish a blinded and randomised clinical trial. The low numbers of COVID cases in Australia in 2020 meant the planned trial in Australia had to be paused. The establishment of a trial depends on Australian and overseas circumstances, and will be communicated when we are in a position to do so.” Dr Wagstaff is the researcher who did the experiment of Ivemectin for COVID.
Recently, there has been a question about the toxicity of Ivermectin. This doubt is understandable as COVID is a new disease and Ivermectin is a repurposed drug for this disease. Chandler, 20182 reported the neurotoxicity of Ivermectin by using VigiBase, an international database of suspected adverse drug reactions, though the number of reported cases suggested that such events are likely rare for Ivermectin. P-glycoprotein drug pump (mdr-1) prevents Ivermectin to cross the blood-brain barrier (BBB) in humans. It is encoded by the multidrug resistance genes (mdr) and the pump is powered by ATP. P-glycoprotein acts as a transmembrane efflux pump which removes drugs from the cell membrane and cytoplasm. It is found in high concentrations in the colon, small intestines and distal small bowel. High levels of P-glycoprotein are also found on the epithelial cells in small biliary ductules, pancreas, kidneys, and adrenal glands3. P-glycoprotein is richly expressed on the subapical surface of the epithelium of the choroid plexus of the brain (which forms the blood-cerebrospinal fluid barrier) as well as the luminal surface of the endothelium of the blood capillaries of the brain (blood-brain barrier). P-glycoprotein is also found in the haemopoietic system, peripheral blood mononuclear cells, macrophages, natural killer, dendritic cells, and T and B lymphocytes.
In the brain, focused ultrasound (FUS), when combined with a microbubble agent, has the ability to temporarily disrupt blood-brain barrier (BBB)4. Overexpression P-glycoprotein and other efflux pumps are linked to multi-drug resistance against several anticancer drugs. Doxycycline is an inhibitor of P-glycoprotein in the alpaca for the purpose of maintaining avermectins in the CNS during treatment for Meningeal worms5. In vitro studies revealed that doxycycline was effective at inhibiting the efflux of Ivermectin and Doramectin (minocycline had no effect).
Effects of Ivermectin (IVM) or Diethylcarbamazine (DEC) in Loiasis was reported in a trial. It was known that people who also have Loa loa have had serious bad reactions to Ivermectin. The side effects were not quite significant, with the diarrhea as the dominant side effects of Ivemectin in Loa loa infection, no fatal effect of the two drugs6. Chandler, 2018 reported serious neurological adverse events were initially reported in public health programs in Africa to eliminate onchocerciasis through community-based Ivermectin treatment as cases of encephalopathy and coma were reported in Cameroon and the Democratic Republic of Congo in persons who concomitantly harbored high densities of another filarial species, Loa loa. There were only two fatal cases (7.14%) from 28 cases focused in this study. One fatal case was a patient with a past medical history of giant cell arteritis, treated with prednisone developed sepsis, complicated by multisystem organ failure, after an aortic valve replacement. A diagnosis of S. stercoralis hyperinfection syndrome was made and he was given Ivermectin 12 mg every 48 hours. He received three oral doses followed by two subcutaneous doses. Autopsy revealed an elevated level of Ivermectin in the brain tissue, 14 days after the last dose. There was no report about the combination of Ivermectin and doxycycline in these two fatal cases.
Drugs that are substrates of CYP3A4 enzymes are often also substrates for P-glycoprotein transport, and thus there may be a risk of increased absorption past the blood-brain barrier with concomitant Ivermectin administration. Mutations in the mdr-1 gene, allowing for penetration of Ivermectin into the CNS. Three important confounders for the side effects of Ivermectin7: co-administered drugs with known CNS effects, overdosing, and evidence of secondary impairment of the blood-brain barrier. In COVID, some studies have advised the combination of Ivermectin and doxycycline, as doxycycline can inhibit the efflux of Ivermectin. With given dosage in early treatment for COVID, we shouldn’t see any overdose.
Hence, Ivermectin is a safe drug for COVID. If we compare COVID vaccines safety with Ivermectin, it will be really a bias. With thousands in fatal cases connected to the COVID vaccines in almost 1 year of the vaccine campaign, Ivermectin cases (with 40 years of history in medical use) from the VigiBase are incomparable.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929173/
https://clinicaltrials.gov/ct2/show/study/NCT01593722