Ivermectin is primarily an anti-parasitic drug, developed and registered for use in humans and animals in many countries. It is not registered for human use in South Africa. It’s been around for many years but has come to attention as one of the drugs – like dexamethasone and hydroxychloroquine – that have been investigated for possible benefits and repurposing in relation to Covid-19.
A number of these studies are still under way.
However, because of initial positive indications – evident from trials, past analyses and its current “off-label” use – a movement has formed demanding its use and claiming it is a cheap “wonder drug” with the potential to save many lives if sanctioned by regulatory authorities.
In South Africa, an ivermectin interest group has sprung up and there is advocacy and argument for the drug on social media. It is reportedly already being used widely, in some cases prescribed by doctors and in others obtained and used without medical supervision.
One doctor told me how “all his veterinary friends were now out of stock”. A qualified doctor, who sees hundreds of patients a week, admitted he is taking it because it is “the only protection he has in wards, given the inadequacy of quality PPE supplies, the pressure caused by the second wave and the government’s delay in initiating a vaccine programme”.
However, while there are reports of benefits, there are also reports of overdoses and people profiteering by selling pills for up to R500 a pop. According to Maverick Citizen’s Eastern Cape writer, Estelle Ellis: “Here in Port Elizabeth people are buying the ivermectin cattle dip and putting it in the bath. You can buy it at the co-op. There is even a prescription going around on how much you are supposed to use. It will probably not be long before we see more cases of ivermectin toxicity than Covid-19.”
According to Andy Gray, one of South Africa’s most respected pharmacologists, who is globally recognised, the demand is being driven by a combination of genuine desperation, especially among GPs and intensivists on the frontline of care, “as well as some less visible commercial interests”. Gray says the drug is also being promoted by respected physicians, often well meaning but whose words, PowerPoint slides and YouTube videos are being seized on and sometimes used selectively and out of context.
However, up to now the South African Health Products Regulatory Authority (SAHPRA) has taken a firm stance to prohibit its use as it awaits further evidence (see its latest statement here). The Ministerial Advisory Committee on Covid-19 has taken a similar stand in a recent memo. However, SAHPRA has said it will consider s21 applications (which allow use of a drug in exceptional circumstances), but says it has not received any yet.
SAHPRA has been criticised, including by Dr Nathi Mdladla, whose op-ed on why ivermectin should be allowed for compassionate use – properly prescribed and controlled by health workers – we are publishing today to set out the perspective of a number of healthcare workers on this issue.
Mdladla, a frontline intensive care doctor at Dr George Mukhari Academic Hospital, thinks there are strong medical and evidentiary grounds to make ivermectin available for compassionate use:
“For a drug that has been dosed almost 3.5 billion times since it came to existence, its side-effects are obviously negligible. We have more dangerous drugs with way more common side-effects than ivermectin that are being used routinely, including many of our antiretrovirals that save lives.”
He argues that “preliminary results from the Unitaid meta-analysis have already been presented by many people, including Dr/Professor Pierre Kory and Professor Paul Marik of the Front Line Critical Care COVID (FLCCV) Alliance; as well as the principal investigator of the Unitaid-funded review, Dr Andrew Hill from the University of Liverpool. The findings, from more than 50 trials including 11 randomised control trials (RCTs) of good quality and significant numbers, have yielded 7,100 patients, enough for a robust meta-analysis.”
Mdladla accepts that the evidence is not conclusive, but given the drug’s safety profile and ready availability, he concludes:
“What would our justification be if ivermectin is eventually proven to be effective when the evidence has been around all along? Will the excuse for waiting for large multicentre RCTs be justifiable to the thousands of families who have lost their loved ones?”
Between a rock and a hard place
In this context SAHPRA once again finds itself between a rock and a hard place.
Medicine regulatory authorities are critical to ensure that those medicines that do reach our health system are safe and effective. They protect us against quacks, false claims and profiteering from unproven medicines. Unfortunately, they don’t protect us from profiteering from registered medicines, like oncology drugs, and that is still a bone of contention between SAHPRA and health rights activists.
In South Africa, SAHPRA, a statutory body, fulfils a legal and ethical mandate to ensure the efficacy and safety of all drugs in the country. Its work is vital to realising Section 27 of our Constitution – the “right of everyone to have access to healthcare services”.
Unfortunately, though, its budget is too way too small. Partly as a result of this, medicines regulation in South Africa has an unhappy history.
Its predecessor, the Medicines Control Council (MCC), and now SAPHRA have been criticised for allowing huge backlogs in applications for medicines. Twenty years ago, the Treatment Action Campaign took on the MCC for the delay in allowing the antiretroviral drugs Nevirapine and AZT to be used to prevent mother-to-child HIV transmission, despite clinical trials showing their efficacy. It also illegally imported a generic drug, Fluconazole, in defiance of the MCC’s refusal to permit its use. There was a belief that the procrastination was political and linked to pressure from then health minister Manto Tshabalala-Msimang.
For all these reasons public trust is low and SAHPRA’s transparency and public engagement even worse.
Maverick Citizen respects, protects and promotes the crucial role of SAHPRA in ensuring the efficacy and safety of medicines. Covid-19 poses different issues to HIV. However, ivermectin use is clearly an issue that needs informed and open debate, rather than being driven underground.
SAHPRA acknowledges that ivermectin is being used widely and has taken action to try and stop this. The concern, however, is that what one doctor called the “heavy-handed action and punitive approach of SAHPRA”, without building public understanding, may be driving the drug underground and creating higher safety risks.
Maverick Citizen consulted a number of senior doctors and it’s clear that the issue is complex. They all agree the drug is safe, that its profile is known and it’s not an “experimental drug”. The danger is that it will be abused or overdosed. Some argue this is why it would be better for SAHPRA to open a window that regulates use by named health professionals through s21 authorisations, rather than acknowledge its underground use in a way SAHPRA has no control over. According to Andy Gray, because it’s not registered for human use here, the drugs currently being used are either being imported illegally or are veterinary products. In other countries its registration opens the door to off-label use, including for Covid-19 (even if not recommended by health authorities).
Senior doctors also agree “there is a potential that more evidence will show that its advocates are right”. However, they warn against those who are suggesting definitively that the drug works, pointing out that some of the trials on which claims are based were poorly constructed and that anecdotal claims lack the rigour of RCTs.
However, they expect that within weeks reports from trials under way will yield greater certainty.
In the light of this, Mdladla’s article cannot be brushed aside, but his views must be balanced and considered in context. It is also incumbent on all of us to hold these debates in public, to be responsible in what we say and claim and ensure that our assertions are evidence based. One thing beyond dispute is that, as increasing numbers of patients die in hospital corridors as our ICUs fill up, there is an unmet need for vaccine rollout and therapeutic interventions that is urgent and immediate. DM/MC