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Sifelani Tsiko
Agric, Environment & Innovations Editor
As of this week, there were more than 477 000 deaths and over 9,2 million confirmed cases of coronavirus across the world, while 4 630 880 people have recovered. Globally, doctors, scientists and governments are on the lookout for safe and effective treatments to help those who are sick.
Sifelani Tsiko (ST), our Agric, Environment & Innovations Editor, speaks to Ms Pinky Manyau (PM), a University of Zimbabwe clinical pharmacologist, on the potential of the low-dose steroid treatment dexamethasone in the rapid management of the virus to reduce case fatality and improve the recovery rate. Her response reflects her personal views.
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ST: For the first time ever since the novel coronavirus broke out last December, a team of researchers at Oxford University has found that a cheap and widely available drug called Dexamethasone could be effective in the treatment of severe forms of Covid-19. Could you comment briefly on the findings and what this could mean in the search for Covid-19 drugs.
PM: These findings are very interesting, especially considering that the use of dexamethasone for viral pneumonia is controversial. In fact, the May 2020 WHO interim guidance for Covid-19 was against the use of dexamethasone and other drugs in its class for Covid-19. However, intuitively, these findings make sense.
There was a 20 to 30 percent reduction in the risk of mortality in subsets of severely ill Covid-19 patients. Practically speaking, you would need to treat eight patients on a ventilator and 25 patients receiving supplemental oxygen with dexamethasone to avoid one death.
These findings reiterate the importance of supportive treatment which seems to be overshadowed by the search for antiviral agents. With respect to future research, dexamethasone belongs to a class of drugs called corticosteroids (drugs that lowers inflammation in the body).
Whilst it is cheap, there is a cheaper option called prednisolone which may be worth taking a look at. Additionally, as the toolkit for Covid-19 treatment grows, further trials can assess the benefit of combining efficacious treatments with different mechanisms of action, for example, remdesivir and dexamethasone.
ST: Have the Oxford results of the trial been published in any peer-reviewed journal?
PM: No, a peer-reviewed publication is not available as yet. Currently, there is a non-peer reviewed pre-print article available. For those who are interested, it’s a good read which calibrates one’s perception of the treatment.
ST: The dexamethasone drug has been around since the early 1960s. Can you tell us briefly what it is and what it has been used for over the decades?
PM: Dexamethasone belongs to a class of drugs called glucocorticoids which are synthetic steroid hormones. Glucocorticoids have multiple actions which include anti-inflammatory effects and regulation of metabolism and appetite.
When a person’s natural glucocorticoids cannot cope with high levels of inflammation, synthetic versions like dexamethasone can be used.
Dexamethasone has been used for a wide range of illnesses which are caused by hyper-inflammation such as asthma, arthritis and allergic reactions. It has also been effective in cancer management to treat the cancer itself, and as a supportive treatment for nausea, vomiting and pain.
ST: What then makes it so useful now in fighting off the worst effects of Covid -19?
PM: Dexamethasone reduced the risk of mortality in patients who were on a ventilator and those requiring supplemental oxygen therapy. These patients are those who are likely to be having trouble breathing due to the ‘cytokine storm’.
The cytokine storm occurs when the immune system overreacts to the viral invasion and begins to damage body tissues in the process of trying to clear the virus, you could call it ‘collateral damage.’ Dexamethasone is an anti-inflammatory drug which helps quieten the storm.
ST: Pharmaceutical experts say dexamethasone is cheap and costs about US$6 per day for a seven to 10-day treatment. Do you think people from poor backgrounds in most developing countries can have access to the drug? How does the cost compare to ARVs, cancer and diabetes treatments?
PM: If I limit the comparison to medicines in our national standard treatment guidelines for common conditions like hypertension and diabetes, chronic medication for one month costs US$1 to US$10.
Cancer treatments vary widely and can cost as little as US$50 to thousands for one treatment cycle. If dexamethasone is made available at US$6 per day, then a course will cost up to US$60, which I think is out of the reach of many.
Alternatively, our clinicians could conduct research assessing prednisolone which is very similar to dexamethasone. The dose of 6mg of dexamethasone which was used in the trial is equivalent to 40mg of prednisolone.
The trial protocol actually substituted prednisolone for patients who had conditions which prevented them from taking dexamethasone. From this, one can assume that prednisolone is a suitable substitute for dexamethasone and it costs approximate US$0.50 per day.
Hence, prednisolone may be an even cheaper alternative which is widely available in Zimbabwe.
ST: At its peak, Zimbabwe’s largest pharmaceuticals manufacturer, CAPS Pharmaceuticals, used to make dexamethasone, even exporting to neighbouring countries. As efforts to revive the company take shape, do you think Zimbabwe has the capacity to manufacture the drug locally? What does it take to manufacture the drug?
PM: I think that Zimbabwe does have the capacity to manufacture the drug. As you mentioned, CAPS Pharmaceuticals used to produce dexamethasone tablets, so the fundamentals are in place.
By fundamentals I mean that they have a formulation and an established manufacturing process which is approved by regulators in the region.
Therefore, any increase in demand in the market can be met without substantial delays from product development and regulatory processes. The only challenge that I foresee is shortage of the active pharmaceutical ingredient dexamethasone.
Countries who manufacture the raw ingredient and finished products are likely to stockpile and restrict export.
This was the case when people thought that hydroxychloroquine was an effective Covid-19 treatment.
Countries stockpiled the medication and large pharmaceutical exporters like India banned exportation of the raw material and formulations. We will probably see the same thing happening for dexamethasone.
ST: What do you think needs to be done to ensure the availability and access of the dexamethasone drugs in the country’s health sector in the near future?
PM: Local availability of dexamethasone has been driven by market forces. Overall, the demand dexamethasone is relatively low, and, therefore, supply has also been low. Use of oral formulations is generally limited to cancer patients and the intravenous formulation is restricted to hospitalised patients.
If demand for dexamethasone increases, I am sure local pharmaceutical manufacturers and wholesalers will meet the challenge. In the short-term, pharmaceutical wholesalers can increase importation of finished products, while manufacturers with existing registered formulations restart and scale-up manufacture.
Ideally, local products should eventually satisfy the market.
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