key: cord-0901632-1m071lab authors: Gandhi, Zainab; Mansuri, Zeeshan; Bansod, Snehal title: Potential Interactions of Remdesivir with Pulmonary Drugs: a Covid-19 Perspective date: 2020-08-21 journal: SN Compr Clin Med DOI: 10.1007/s42399-020-00462-2 sha: 710130636e1b168a7ef14f178e418b71861c3592 doc_id: 901632 cord_uid: 1m071lab 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. 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) . Remdesivir has a low risk of significant pharmacodynamic interactions [6] . 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 CYP 2C9, 4, 5, it has the potential of interaction with remdesivir. Although remdesivir causes inhibition of CYP 3A4, it is not expected to affect bosentan's metabolism. However, as bosentan is an inducer of CYP 3A4, it can potentially cause decreased levels of remdesivir [4] . Remdesivir does not interact with ambrisentan, epoprostenol, iloprost, macitentan, riociguat, selexipag, sildenafil, tadalafil, and treprostinil [6] . Remdesivir has no known interactions with any bronchodilators and beta-blockers and antivirals including oseltamivir [6] . Metamizole is a nonsteroidal antiinflammatory drug (NSAID) used for chronic pain management in many countries. Metamizole gets hydrolyzed to 4methylaminoantipyrine which is a substrate for CYP 3A4, 2B6, 2C8, and 2C9. No effect is expected due to remdesivir as it inhibits CYP3A4. However, as metamizole induces CYP3A4 moderately and CYP2B6 strongly in vitro, it can lead to depleted levels of remdesivir [6] . In summary, since remdesivir is metabolized quickly, the risk of interactions is exceptionally low. As we deal with critically ill COVID-19 patients with underlying comorbidities, clinicians need to be careful about the co-administration of various drugs with remdesivir as listed above and keep an eye out for new data that comes out. Conflict of Interest The authors declare that they have no conflict of interest. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Leads to decreased levels of remdesivir by rapid clearance. There is no effect on the metabolism of metamizole due to inhibition of CYP3A4 by remdesivir Rifampicin Rifampicin strongly induces CYP3A4 and P-gp Leads to decreased levels of remdesivir by rapid clearance. There is no effect on the metabolism of rifampicin Rifabutin Rifabutin strongly induces CYP3A4 Leads to decreased levels of remdesivir by rapid clearance. There is no effect on the metabolism of rifabutin Rifapentine Rifapentine strongly induces CYP3A4 Leads to decreased levels of remdesivir by rapid clearance. There is no effect on metabolism of rifapentine Carbamazepine Carbamazepine strongly induces CYP3A4 and UGT2B7 Leads to decreased levels of remdesivir, no effect on carbamazepine as remdesivir does not affect UGT's Phenytoin Phenytoin strongly induces CYP3A4 Leads to decreased levels of remdesivir. There is no effect on phenytoin as CYP2C9 metabolizes it Phenobarbitone Phenobarbitone strongly induces CYP3A4 Leads to decreased levels of remdesivir. There is no effect on phenytoin as CYP2C19, and CYP2C29 metabolize it Primidone Primidone is metabolized to phenobarbital and thus induces CYP3A4 Leads to decreased levels of remdesivir. There is no effect on primidone by inhibition of CYP3A4 by remdesivir as it is not metabolized by it St John's wort St John's wort strongly induces CYP3A4 It can lead to decreased levels of remdesivir. No effect is observed on metabolism of ST John's wort Dexamethasone Dexamethasone strongly induces CYP3A4 It can lead to decreased levels of remdesivir by rapid clearance but no effect on metabolism of dexamethasone Betamethasone Betamethasone strongly induces CYP3A4 It can lead to decreased levels of remdesivir by rapid clearance but no effect on metabolism of betamethasone Mechanism of inhibition of Ebola virus RNAdependent RNA polymerase by remdesivir A precision medicine approach to SARS-CoV-2 pandemic management Clinical applications of personalized medicine: a new paradigm and challenge Coronavirus disease 2019 treatment: a review of early and emerging options Remdesivir in COVID-19: a critical review of pharmacology, pre-clinical and clinical studies Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4