- Local experts stress that evidence that ivermectin can treat or prevent Covid-19 is still lacking
- If you are going to use ivermectin for Covid-19, you should rely on medical advice and have a doctor prescribe it, they say
- The WHO also currently does not recommend the use of the drug to treat Covid-19
Ivermectin, an antiparasitic drug, has been in the spotlight over the last few months, amid debate over its suitability as a possible treatment and prophylaxis (preventive) for Covid-19.
While a small number of studies have signalled that it may be beneficial in Covid cases, we have to consider that the parasiticide is a complex compound and that the evidence, so far, is inconclusive and based on studies done in vitro (in lab settings), and not in humans, said Professor Natalie Schellack, Head of the Department of Pharmacology at the University of Pretoria.
Schellack was part of a panel of speakers for a webinar hosted by the University of Pretoria on 30 April, where the use of ivermectin to treat Covid-19 was discussed.
(In vitro studies take place in a controlled environment, such as a test tube or petri dish in a laboratory. In contrast, in vivo studies refer to tests and experiments that are performed in or on a whole living organism, such as a human, laboratory animal, or plant, explains Medical News Today.)
Schellack acknowledged the promising results of the Australian study, published in 2020, in which five researchers found that constant exposure of ivermectin in an in vitro setting, and at a certain concentration, killed almost all SARS-CoV-2 viral particles within 48 hours.
“But what is important is that ivermectin is such a complex compound,” added Schellack, “So translating that from one compartment – an in vitro model – to a complex human compartment … we don’t have conclusive evidence that it has the same effects.”
Ivermectin is included on the World Health Organization’s (WHO) list of essential medicines for several parasitic diseases. However, the agency advises against its use for Covid.
On 31 March 2021, the WHO released a statement: “The current evidence on the use of ivermectin to treat Covid-19 patients is inconclusive. Until more data are available, WHO recommends that the drug only be used within clinical trials."
This recommendation, which applies to patients with Covid-19 of any disease severity, is now part of WHO’s guidelines on Covid-19 treatments.
Their guidance was posted after an independent, international panel of experts reviewed the data from 16 clinical trials that assessed whether ivermectin reduces mortality, the need for mechanical ventilation, the need for hospital admission and the time to clinical improvement in Covid patients. The team found that the evidence was of “very low certainty”, due to a number of study limitations including small study samples.
Locally, the University of the Free State’s clinical trial arm is conducting a study to assess the efficacy of ivermectin for Covid disease, Health24 reported in January.
Inhibiting viral infection
In some of the human clinical trials, a dosage of around 200 to 300 micrograms (mcg) per kilogram (kg) of ivermectin was administered to participants, said Schellack, and 30 and 60 mcg were given over the course of three to five days in some specific pharmacokinetic studies. The important aim in the context of Covid, however, is for it to inhibit viral replication. To achieve this, an effective concentration of the drug, as seen in the lab studies, is needed.
But if you have too much of the drug in your system it might not cross the blood-brain barrier, which is essential for targeting viral replication, explained Schellack.
Professor Vinny Naidoo, a specialist veterinary pharmacologist and Dean of the Faculty of Veterinary Science of the University of Pretoria, touched on the side effects of the drug on animals and humans. There are vast interspecies differences between animals and humans, he explained.
For example, certain dog breeds don’t have blood-brain barrier pumps, which can lead to a high concentration of drugs reaching the brain.
“And in these animals, at the normal recommended dose, they can slip into a coma. And a lot of them die. That's the most serious side effect that can occur,” said Naidoo.
He added: “The drug is not necessarily safe in mammals – it’s just safe because it doesn’t get to the brain.”
But since Covid is considered a hyper-inflammatory condition, an incorrect dosage of ivermectin can result in an accumulation of it in the brain and a person could end up having severe side effects, explained Naidoo.
Apart from the dangerous side effects, another concern Schellack highlighted was the large rollout of antiretrovirals among South Africa’s population.
“We are worried about all the other drug interactions when we are using this drug outside of its intended uses,” she said.
Lethal to humans?
When researchers looked at some of these first-phase studies, the doses were deemed to be safe, said Schellack.
“But what is happening currently in a condition such as Covid, is that the body is in a hyper-inflammatory state (a cytokine storm),” which means that even if you’re given a low dose, there is a potential for drug toxicity.
Prophylactic use of ivermectin for Covid
“There have been pockets of countries in the world that rolled out ivermectin for the reduction in Covid-19, and we really haven’t seen any conclusive evidence for that,” said Schellack.
Some South American countries have reported success, but the methodology used in those studies were questionable and that’s why the rest of the world has not adopted that practice, she added.
According to Schellack, the drug's use for Covid has led to "a great division in the scientific community".
"Some of the doctors and colleagues globally are really hopeful because of the signal," she said, adding: "It’s the drug that has caused the biggest division between scientists."
We need more clinical trials
“If it’s not being prescribed to you at a dose, and if no one knows what comorbid conditions you have, and if we don’t have the correct drug formulations, you might be taking only the side effects, rather than the effects, so we really do need more clinical trials,” stressed Schellack.
For now, she urged the public to be wary of taking drugs for which there's a lack of clinical evidence to guide us regarding its usage.
Have a doctor prescribe it
Although ivermectin remains one of the most effective anti-parasitic drugs available on the veterinary market, Naidoo’s recommendation to the public on the use of the drug for Covid is also one of caution.
“The question I’ve been getting often is, ‘Can I buy veterinary ivermectin because it’s readily available, and put myself on it?’ and my answer remains ‘absolutely not’.
“We don’t know anything about these formulations in people. To take a drug in which we absolutely know nothing about is unsafe."
Naidoo says in cases where ivermectin (for human use) is to be used, medical advice must be relied on and a doctor would have to prescribe it. The case would also have to be monitored "because side effects can be nasty".
Access to ivermectin for Covid in SA
In January 2021, the South African Health Products Regulatory Authority (Sahpra) introduced its Ivermectin Controlled Compassionate Use Programme, allowing the drug to be used in special circumstances, if applied for (and approved by Sahpra), by a relevant healthcare practitioner.
A doctor who wishes to use ivermectin for treating a patient with Covid would have to apply via the Section 21 online submission portal facility, Health24 previously reported. This provision would help to monitor the progress of the patient to see whether there are positive or negative outcomes, the regulatory authority said.