Highlights

Abstract

Abbreviations

Keywords

۱٫ Introduction

۲٫ Mechanisms of action of COVID-19 candidate drugs

۳٫ Potential drug-drug interactions between ASMs and COVID-19 candidate drugs

۴٫ Potential drug interactions between ASMs and antipyretic and anti-inflammatory drugs concomitantly used in COVID-19 patients

۵٫ Conclusion

Data availability statement

References

Abstract

In regard to the global pandemic of COVID-19, it seems that persons with epilepsy (PWE) are not more vulnerable to get infected by SARS-CoV-2, nor are they more susceptible to a critical course of the disease. However, management of acute seizures in patients with COVID-19 as well as management of PWE and COVID-19 needs to consider potential drug-drug interactions between antiseizure drugs and candidate drugs currently assessed as therapeutic options for COVID-19. Repurposing of several licensed and investigational drugs is discussed for therapeutic management of COVID-19. While for none of these approaches, efficacy and tolerability has been confirmed yet in sufficiently powered and controlled clinical studies, testing is ongoing with multiple clinical trials worldwide. Here, we have summarized the possible mechanisms of action of drugs currently considered as potential therapeutic options for COVID-19 management along with possible and confirmed drug-drug interactions that should be considered for a combination of antiseizure drugs and COVID-19 candidate drugs. Our review suggests that potential drug-drug interactions should be taken into account with drugs such as chloroquine/hydroxychloroquine and lopinavir/ritonavir while remdesivir and tocilizumab may be less prone to clinically relevant interactions with ASMs.

۱٫ Introduction

The catastrophic global pandemic of Coronavirus disease 2019 (COVID-19) has put large parts of the world on a transient standstill. COVID-19 was first discovered in December 2019 and the causative agent was a novel subtype of beta-coronaviruses, known as SARS-CoV-2 (Rothan and Byrareddy, 2020). The novel coronavirus is an enveloped non-segmented positive-sense RNA virus (Richman et al., 2016) that was transmitted to humans via zoonotic transmission, similar to its precursors, severe acute respiratory syndrome coronavirus (SARS-CoV) (Ksiazek et al., 2003) and the Middle East respiratory syndrome coronavirus (MERS-CoV) (Zaki et al., 2012). These viruses primarily affect the respiratory system, however, clinical literature also provides evidence for neuroinvasive and neurotropic properties of SARS-CoV-2 (Carod-Artal, 2020; Li et al., 2020b; Najjar et al., 2020). Neurological symptoms reported in patients with COVID-19 include febrile seizures, status epilepticus and complications including encephalopathy, cerebral haemorrhage (Asadi-Pooya, 2020; Asadi-Pooya and Simani, 2020; Carod-Artal, 2020; Yin et al., 2020). These clinical manifestations suggest that people with neurological disorders may be more vulnerable to experience severe symptoms of COVID-19 disease. However, that does not seem to be the case. The International League Against Epilepsy (ILAE) has informed that persons with epilepsy (PWE) are not likely to be more susceptible to get COVID-19 nor are they inclined to suffer through severe manifestations of SARS-CoV-2 infection (ILAE, 2020). Even if PWE are exposed to SARS-CoV-2, it is unlikely that the frequency of seizures increases (ILAE, 2020). Nevertheless, management of COVID-19 in PWE or with acute reactive seizures requires certain precautions and guidelines to avoid worsening of the condition. In particular, potential drug-drug interaction that may occur on concomitant administration of anti-seizure medication (ASM) along with the drugs for treatment of COVID-19 need to be taken into account.