A pharmacist holds the anti-parasite drug ivermectin in Santa Cruz, Bolivia, May 19, 2020. Photo: Reuters/Rodrigo Urzagasti
New Delhi: As several Indian states continue to prescribe ivermectin, the WHO’s chief scientist Soumya Swaminathan on Tuesday tweeted that the UN agency recommends against the use of the drug to treat COVID-19 patients except within clinical trials. Included in the tweet was a press release issued by the company that manufactures the drug, Merck, saying it has not found any evidence to support ivermectin’s use in treating COVID-19.
“Safety and efficacy are important when using any drug for a new indication,” Swaminathan said in her tweet.
Safety and efficacy are important when using any drug for a new indication. @WHO recommends against the use of ivermectin for #COVID19 except within clinical trials https://t.co/dSbDiW5tCW
— Soumya Swaminathan (@doctorsoumya) May 10, 2021
Her tweet came a day after the Government of Goa announced that it would give all people older than 18 years ivermectin – irrespective of whether they have COVID-19 to “bring down mortality”. The medical evidence says this is not possible. The state’s health minister Vishwajit Rane said on Monday that patients will be given 12 mg of ivermectin for five days.
A COVID-19 case management protocol issued by the new Tamil Nadu government also prescribes 12 mg of ivermectin for three days for people with all forms of COVID-19 – mild, moderate and severe. The protocol also recommends an antibiotic (azithromycin), whose use has also become irrational, experts have said.
For example, as Dr Amulya Gupta wrote for The Wire Science last week:
For example, antibiotics like azithromycin and doxycycline are still commonly advised for COVID-19 despite large clinical trials having found no evidence for their use, and despite the WHO’s persistent messaging.
These medicines are supposed to be useful in patients with specific clinical features and a high risk of developing a superimposed bacterial infection over the standard COVID-19 pneumonia. But many practitioners have been prescribing them as a blanket therapy for all COVID-19 patients.
These two states have also been joined by Uttar Pradesh, Uttarakhand and Karnataka.
Pressure to prescribe
As The Wire Science has reported, doctors across the country are being pressured into giving drugs – not just ivermectin but also remdesivir and tocilizumab – despite knowing that they are not effective against all forms of COVID-19 and irrespective of the patient’s medical history.
Dr Sumit Ray, head of the department of critical care at the Holy Family Hospital in New Delhi, told IndiaSpend that he has prescribed ivermectin only because of the pressure, but never to a patient in the ICU. He said he had prescribed it to people in the OPD and also asked them to stop it if they felt nauseous because “it is probably not going to benefit” them. “But I don’t think it benefits anyone. The evidence is very, very weak for it, and [for] Fabiflu1, there is no evidence,” he added. “There were two studies which were done which had very strong bias” and were “very poor quality studies.”
In her tweet, Swaminathan attached a press release the German pharmaceutical company Merck, whose scientists found the compound from which ivermectin is derived, issued in February this year.
The release says the company’s scientists are carefully examining findings of all available and emerging studies of ivermectin for treating COVID-19 for evidence of efficacy and safety. To date, they have not found any scientific basis for a potential therapeutic effect against COVID-19, nor any meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19. Merck said that its analysis has, however, identified “a concerning lack of safety data in the majority of studies”.
“We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information,” it said.
Ivermectin is indicated to treat intestinal strongyloidiasis, a disease caused by a parasite that can abdominal pain, diarrhoea and weight loss, and for treating onchocerciasis, or river blindness, another parasitic disease that can result in blindness but also causes severe itching and bumps under the skin. Merck’s release also indicated the adverse reactions documented during clinical trials when ivermectin is used to treat strongyloidiasis and onchocerciasis.
Merck said ivermectin shoudln’t be used during pregnancy since safety in pregnancy has not been established. It added that ivermectin is excreted in human milk in low concentrations, so mothers who intend to breastfeed should only consider taking it when the risk of delayed treatment to the mother outweighs the possible risk to the newborn. Safety and efficacy in paediatric patients weighing less than 15 kg also haven’t been established, it said.
However, it is not clear why Dr Swaminathan chose to cite Merck. According to an older WHO article, “Merck’s patent on ivermectin expired in 1996, though it was extended for different periods in various countries. Thus, other companies’ ivermectin preparations are now commercially available.”
As such, in discouraging its use, Merck may have a potential conflict of interest. At least this is the argument that has emerged in different publications, with authors alleging that pharma companies are blocking ivermectin’s entry into the market so that vaccines remain profitable. But Dr Lancelot Pinto, a pulmonologist at Hinduja Hospital, Mumbai, told The Swaddle “that this is a common conspiracy theory in India too, especially when it comes to adding drugs to treatment protocols”, and that “Everyone has their own story.” He dismissed them and said that there is as yet no evidence to prove ivermectin is effective against COVID-19.
It is also notable that what we currently know about ivermectin, and its usefulness against some neglected tropical diseases, is based on the small doses in which it is currently administered. A 2009 study found that to treat strongyloidiasis, 200 µg/kg of ivermectin would be needed – 13 mg for a person weighing 65 kg. This is the largest dose currently approved.
Treating COVID-19 could require thrice as much ivermectin, which would bring the dosage outside regulatory limits as well as raise questions about potential toxicity effects. This is why the authors of an analysis published in 2020 said:
As we previously showed, that ivermectin is a non-selective inhibitor of three important mammalian P-type ATPase at similar micromolar concentrations, we have to be concerned with putative important adverse effects that this drug could produce at the higher than usual doses that would be necessary for treating COVID-19 patients. As a result, a phase 1 study is absolutely needed before using ivermectin since a recent meta-analysis concluded that there are not enough data to support a recommendation for its use in higher-than-approved doses. (emphasis added)
But as it happens, in the last few days, websites of several Indian media organisations have republished an article by the news agency IANS that says “global ivermectin use can end the COVID-19 pandemic”, and cites a purportedly peer-reviewed study. The first author of this study is Pierre Kory, a pulmonary and critical care specialist whose claims that ivermectin is a “wonder drug” have been fact-checked to be false. Another author of the study, Paul E. Marik, has also pushed the drug as a ‘miracle cure’ for COVID-19 and has written another paper reviewing ivermectin; it included references to debunked papers.
The Scientist reported that the paper the IANS report cited had initially been accepted for publishing by the editors of Frontiers in Pharmacology, and was abstract form by the journal. But the editors subsequently took the paper down on March 1 after they determined that it contained “unsubstantiated claims and violated the journal’s editorial policies”.
A statement issued by the journal’s chief executive editor, Frederick Fenter, said that “the authors promoted their own specific ivermectin-based treatment, which is inappropriate for a review article and against our editorial policies. In our view, this paper does not offer an objective nor balanced scientific contribution to the evaluation of ivermectin as a potential treatment for COVID-19.”
One explanation doctors have for why people wish to use even unproven drugs is action bias – a preference to act even if their actions won’t have any effect on the patient’s chances of recovery or survival. As Dr Gupta wrote:
“The fear of death forces recently diagnosed COVID-19 patients to expect long prescriptions and comprehensive advice, even if this information just doesn’t – or shouldn’t – exist. Patients often ask physicians if they are to restrict their diet in any way, and they feel better if the physician points something out and says it should be avoided. The requirement for specific dietary restrictions seldom exists.”
Have you tested positive for COVID-19? Here is a reasonable description of what you can expect to happen next. In case you have any doubts, please consult with your doctor.
Note: This article was originally published on May 11 and was republished at 5:45 pm on May 14, 2021, after including a quote by Dr Lancelot Pinto and the discussion about ivermectin’s dose.
Glenmark’s trade name for favipiravir↩