Potential risk of investigated drugs for the treatment of COVID-19: drugs interactions

Introduction : The coronavirus causes infections in lower respiratory tract and with preceding cases by the Coronavirus of the Severe Acute Respiratory Syndrome (SARS-CoV) and by the virus of the Middle East Respiratory Syndrome (MERS-CoV). It was aimed to investigate the potential interactions, of severe and moderate degrees, of the drugs tested in the treatment of COVID-19 with other drugs and with diseases. Outline : Characterizes itself as a documentary research that use the data base Drugs ® for obtaining the cross information of the data banks with another drugs, according to articles of periodicals indexed in the great searchers PubMed, Science Direct and BVS. For the determination of the drug interaction, there were used only the data which had at least “good documentation” and only the interactions “expressly contraindicated”, “major” and “moderate”, the mild interactions were omitted. Results : The hydroxychloroquine and the chloroquine are associated with many drug interactions and with drugs, along to the azithromycin, which also has a high degree of risks. However, the nitazoxanide, the ivermectin and the oseltamivir are in the opposite direction, with small drug interactions and low risks to the treatment safety. The monoclonal antibodies and the antiretrovirals have balanced risk-benefit relation. Implications : Most of the currently investigated drugs in the treatment of COVID-19 show several drug interactions and interactions with pre-existing diseases.


INTRODUCTION
In December 2019, in Wuhan, China, it have been started the reports of a severe idiopathic pneumonia. 1 After, laboratory researches detected the virus, denominated coronovirus. 2 The . 5 The genesis of this virus is unknown, however there are reports that correlate the initial cases to a seafood market, in Wuhan, at where wild animals are commercialized. 6 Due to disease progress in several countries all around the world, on March 11, 2020, the WHO 4 declared the novel coronavirus as a pandemic, once the confirmed cases rose abruptly in divers countries, with serious cases leading to deaths. 7 Infection's pathophysiology is similar to the SARS-CoV, where it happens a series of inflammatory responses with risk group persons getting worse, such as cardiac patients, diabetics, the elderly. 8 The main symptoms are: fever, dry cough and dyspnea.
Generally, the incubation period ranges 2 to 14 days after the infection. 9 As to the therapeutics, there emerged studies Other alternatives with more secure potential were tested and employed on COVID- 19  For the determination of the drug interaction, there were used only the data available in the Drugs ® of at least "good documentation" and only the interactions "expressly contraindicated", "major" and "moderate", the mild interactions were omitted.
The "drugs" used in this study all are commercially available medicaments. There were used, as including criterium, the medicaments investigated in vitro way, in vivo or clinically for the COVID-19, whether for prophylaxis or treatment. There were used, as excluding criteria, the medicaments used in the disease A2 treatment stage for treating complications.   The Table 3 Table 4 -Potential interactions of the nitazoxanide with drugs and diseases.

Medicaments Responses
Valproic Acid ++ The nitazoxanide can increase the bioavailability of the valproic acid
The Table 5 shows the potential risks of using

DISCUSSION
The Hydroxychloroquine (HZQ) has been widely studied on COVID-19 treatment, since the precociuous 10 one as the late one, 11 with the improvement by its use, however, the doubt defines the current scenario, once a lot of another studies refute the efficiency of those, 12  Many studies points out the AZT as one of the drugs with higher therapeutic potential in the treatment of the COVID-19, by this reason it is employed in the first line of treatment in medical clinic. [25][26]13 However, its elevated cardiotoxic potential worries, once its possesses risk of QT prolongation and ventricular arrhythmias, just like Table 3 shows and corroborated by the studies. [27][28] The interaction of the AZT with the HZQ and the chloroquine raises the warning sign of that therapy, 29   The Table 4 presents the moderate potential risk of the NZX in promoting enzyme inhibition in the hepatic metabolism of the valproic acid in concomitant use. 36 Besides that, it can promote hyperglycemia in diabetic patients, due the fact of it possessing saccharose in the composition, according to the Brazilian Pharmacopedia, 37 as well as renal and hepatic dysfunctions in patients with commitments in these functions. [38][39] The Ivermectin, another antiparasitic, mentioned in Table 7, which was  Caracteriza-se como uma pesquisa documental que utiliza a base de dados Drugs ® para a obtenção das informações cruzadas dos bancos de dados com outros fármacos, conforme artigos de periódicos indexados nos grandes buscadores PubMed, Science Direct e BVS. Para a determinação de Interação medicamentosa, foram utilizados apenas os dados que dispunham de no mínimo "boa documentação" e apenas as interações "expressamente contraindicadas", "maiores" e "moderadas", as interações leves foram omitidas. Resultados: A hidroxicloroquina e a cloroquina estão associadas a muitas interações medicamentosas e com doenças, juntamente à azitromicina, que também possui um grau alto de riscos. Contudo, a nitazoxanida, ivermectina, oseltamivir estão do outro lado da margem, com pequenas interações e riscos à segurança do tratamento. Os anticorpos monoclonais e os antirretrovirais possuem risco benefício equilibrado. Implicações: A maioria dos medicamentos atualmente investigados no tratamento da COVID-19 apresentam diversas interações medicamentosas e interações com doenças preexistentes.