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Concomitant drug use of nirmatrelvir/ritonavir and CYP3A4-modulating antimicrobial agents: an approach for drug use
  1. Robbert Visscher1,
  2. Nadir Yalçın2,
  3. Izgi Bayraktar2,
  4. Aygin Bayraktar-Ekincioglu2
  1. 1Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
  2. 2Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
  1. Correspondence to Nadir Yalçın, Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey; nadir.yalcin{at}

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Coronavirus disease (COVID-19) and associated infections will still be seen for some time yet in clinical care settings. Current standard of care practices recommend 5 days of treatment with nirmatrelvir/ritonavir for patients who do not use additional oxygen therapy and have a high risk for poor prognosis, regardless of their vaccination status.1 It has been recognised that viral respiratory infections predispose patients to bacterial and mycotic co-infections. In such cases, concomitant treatment with nirmatrelvir/ritonavir and antimicrobial agents is indicated.

Nirmatrelvir and ritonavir are both major substrates for cytochrome P450 3A4 (CYP3A4).2 Additionally, ritonavir is a potent CYP3A4 inhibitor, which inhibits its own elimination.2 Similarly, several antibiotics and antifungal agents are known to be both modulators and substrates for CYP3A4. Therefore, such combinations result in bidirectional drug-drug interactions (DDIs), where serum concentrations of each drug influence the metabolism of the other. This could increase the risk of adverse drug events. For nirmatrelvir/ritonavir, these include nausea, vomiting, diarrhoea and an increase in transaminases.2 As this medicine is relatively new, not all of its possible side effects …

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  • Contributors Conceptualisation, RV and NY; investigation, IB; resources, NY and IB; writing—original draft preparation, RV and IB; writing—review and editing, NY and ABE; supervision, ABE.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.