INTRODUCTION:

Dexamethasone or MK-125, fig. 1 (C₂₂H₂₉FO₅) is a fluorinated corticosteroid used primarily to treat various allergic diseases and rheumatism, as well as endocrine diseases, skin diseases, allergies, ophthalmic, respiratory, gastrointestinal, tumors, hematological, and others. It was approved by the US Food and Drug Administration on 30^th October 1958 ¹.

Fig. 1: Chemical structure of Dexamethasone.

At the beginning of the outbreak, the World Health Organization and many countries warned against treating coronavirus patients with steroids. Some experts have been concerned about the frequent evidence of steroid therapy because it is understood that these medications inhibit the immune system, which can benefit patients whose lungs are compromised by an overactive immune response in serious cases².

Later and according to preliminary clinical findings shared between the World Health Organization and the United Kingdom, dexamethasone could be lifesaving for critical patients with SARS-CoV-2. Dexamethasone was the assessment by the FDA on 16^th June 2020 for the treatment coronavirus. It was found that treatment reduces deaths by one-third of patients who use ventilators, while the percentage decreased to one fifth for patients who only required oxygen. This benefit was observed only in severe cases of SARS-CoV-2 but it has not been observed with milder cases³.

As there are no suitable, approved, or available alternative treatments, the Food and Drug Administration (FDA) welcomed using of remdesivir to treat emergency for suspected or laboratory-confirmed cases in adults and children with low blood oxygen levels or required more intensive breathing support by ventilators⁴.

Remdesivir, fig. 2 (C₂₇H₃₅N₆O₈P) is a nucleoside analog used to inhibit the enzyme (RNA-dependent RNA polymerase) that the virus uses to replicate. It is usually given at a dose of 200mg/day for a patient weight of > 40kg and 5mg/kg for a patient weight of < 40kg. Remdesivir has been used to cure Ebola virus for the first time since 2016. The RNA viruses, including the family of coronave viruses, were subsequently treated, as SARS and MERS-CoV were eligible in 2017.^5,6.

Fig. 2: Chemical structure of remdesivir.

FDA is also authorized remdesivir given by intravenous injection (IV) in adult patients via a single loading dose (200mg) on the first day of symptoms onset, followed by conservation doses once daily (100mg) from the second day. For paediatrics, the dose should be adjusted according to body weight, and depending on a patient requiring mechanical ventilation, the treatment courses are 10 days and 5 days, respectively⁷.

A 48-year-old man presented to the hospital with shortness of breath, cough, auto-fever, and diarrhoea for 10 days. Nasopharyngeal polymerase chain reaction (PCR) was positive for SARS-CoV-2. His respiratory condition rapidly worsened to the point that additional oxygen was required. He was given hydroxychloroquine and then converted to remdesivir when it became available. Then, methylprednisolone kicked off the suspected cytokine storm. The patient's oxygenation improved significantly over the following days. This case illustrates the role of Remdesivir in treating severe COVID-19 pneumonia. A potential clinical benefit of corticosteroids has also been observed in the context of a suspected cell storm⁸.

Limited evidence about remdesivir protection and efficacy is known. Possible side effects of remdesivir include elevated hepatic enzyme levels as a symptom of inflammation, liver damage and associated reactions such as hypotension, vomiting, nausea, trembling and sweating^9,10. A study concluded that an intravenous remdesivir dosing scheme does not provide a clinical or antiviral impact in critically diseased COVID-19 patients. However, variations of therapeutic importance and numerical decreases in certain clinical parameters were not included in the report^11-14.

To date, remdesivir has been found to shorten the patient's hospitalization but it has no statistically relevant mortality impact. Preliminary findings from the 1059 patients (538 remdesivir assigned and 521 placebo assigned) with randomisation evidence suggest that remdesivir recipients have a mean period of recovery for eleven days, compared with 15 days in placebo recipients. One study revealed that a combination of dexamethasone and remdesivir showed a clinical improvement in 36 out of 53 patients with coronavirus. The mortality rate when using dexamethasone decreased by an average of 17%, while the rate with remdesivir tended to decrease, knowing that these differences were not statistically significantly^15,16.

Although the mechanisms of action of dexamethasone and remdesivir are different, the combination between them can be complementary, because remdesivir slows down virus damage while dexamethasone is associated with hyper inflammation. The combination program is undergoing trials, specifically between remdesivir and the interleukin-6 (IL-6) inhibitor (tocilizumab). Therefore, it is possible to try a combination of dexamethasone with remdesivir, especially in severe cases¹⁷.

Currently, there is no information about what are the side effects of remdesivir, although the US Food and Drug Administration recommends it for treating moderate and severe cases of the pandemic To date, there is no study describing clinical concerns about using combined drugs such as remdesivir and dexamethasone for the treatment of COVID-19, or common interventions that occur in clinical trials.

ACKNOWLEDGEMENT:

The authors are grateful to the College of Medicine, University of Mosul.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

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Received on 21.11.2020 Modified on 30.01.2021

Asian Journal of Pharmaceutical Research. 2021; 11(2):138-140.

DOI: 10.52711/2231-5691.2021.00026