Potential Interactions of Remdesivir with Pulmonary Drugs: a Covid-19 Perspective
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COVID-19
Potential Interactions of Remdesivir with Pulmonary Drugs: a Covid-19 Perspective Zainab Gandhi 1
&
Zeeshan Mansuri 2 & Snehal Bansod 3
Accepted: 13 August 2020 # Springer Nature Switzerland AG 2020
Abstract In this letter, we discuss the potential interactions of remdesivir, the newly approved Covid-19 drug with pulmonary medications. These interactions have been summarized keeping the busy clinician in mind. While remdesivir has proven to be a safe medication generally, we here have enlisted the potential interactions of remdesivir that a clinician needs to be mindful of while prescribing the medication. Keywords Remdesivir . Drug interactions . Pulmonology
For coronavirus, there are various therapeutic regimens under trial. Remdesivir has shown promise in initial studies for treating COVID-19 [1]. The mechanism of action for remdesivir has been studied in vivo and in vitro [1]. It acts by delaying the chain termination of RNA synthesis through competing with ATP for incorporation [1]. It has been studied mainly for the Ebola virus and respiratory syncytial virus, but the broad mechanism of action can be helpful in the treatment for SARS-CoV2 [1]. With the use of precision medicine, we can prevent, mitigate, and provide personalized pharmacologic treatment to the patients [2, 3]. Remdesivir is a substrate of CYP 3A4, CYP 2D6, and CYP 2C8, and its metabolism is mediated by hydrolase activity [4, 5]. The potential co-administration of inhibitors can lead to a potential increase in its levels [4, 5]. As remdesivir is a substrate of CYP 3A4, caution must be taken as it is co-administered
with many drugs, including above, as CYP enzymes are involved in the metabolism of a wide range of medications. However, the initial data coming out shows no harmful effects of these drug-drug interactions, due to its rapid metabolism by hydrolase and esterase [4, 5]. We conducted thorough search of Embase, PubMed, Scopus, PsycINFO, SciELO, and Web of Science. Since the drug is new and the information available is scarce, this commentary aims to review the potential interactions of remdesivir (Table 1).
Pharmacodynamic Interactions Remdesivir has a low risk of significant pharmacodynamic interactions [6].
Zainab Gandhi and Zeeshan Mansuri share equal credit for primary authorship
Pharmacokinetic Interactions
This article is part of the Topical Collection on Covid-19
Steroids like dexamethasone and betamethasone induce CYP3A4 and thus will result in the rapid clearance of remdesivir [4]. Clinicians need to be cautious regarding this interaction. Rifampicin, rifabutin, and rifapentine strongly induce CYP3A4 enzyme [7]. These medications are used in the treatment of tuberculosis and leprosy. Co-administration of these medications with remdesivir can lead to rapid clearance and a significant decrease in remdesivir levels [6, 7]. This combination should not be co-administered [6, 7]. Bosentan is a drug primarily used in the treatment of pulmonary arterial hypertension. As it is mainly metabolized by CYP 3A4 and
* Zai
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