Potential drug-drug interactions with nirmatrelvir/ritonavir in
critically ill patients with COVID-19 – a retrospective observational
study
Abstract
Background Nirmatrelvir/ritonavir is recommended for high-risk patients
with COVID-19 to reduce disease progression and mortality. Ritonavir
significantly increases the bioavailability of nirmatrelvir and is the
most potent irreversible cytochrome P 450 3A4 inhibitor in clinical use,
resulting in a substantial risk for drug-drug interactions (DDI). We
aimed to analyze the incidence of potential DDI (pDDI) in critically ill
patients with SARS-CoV-2 infection. 7.2 Methods This is a retrospective
single-center study in a quaternary care center in Northern Germany. We
reviewed electronic health records for demographic characteristics,
comorbid conditions, and medication history. The pre-existing
comedication was screened for pDDI with nirmatrelvir/ritonavir using
publicly available databases. Binary logistic regression was used to
identify patient characteristics associated with pDDI. 7.3 Results Of
500 critically ill patients with SARS-CoV-2 infection, 362 (72.4%)
received pre-existing comedication. A total of 241/500 patients (48.2%)
had a medication history prone to pDDI. Antidiabetics, lipid-lowering
drugs, and anticoagulants were among the most frequently used agents
with a pDDI. Higher age (OR 1.043; 1.028-1.058; p<0.01) and
the number of comorbidities (OR 1.229; 1.119-1.350; p<0.01)
were significantly associated with pDDI. 7.4 Conclusion The very patient
population that may benefit most from treatment with
nirmatrelvir/ritonavir also has the greatest risk of pDDI. Polypharmacy
is frequently present in these patients and a conscientious check of the
comedication is mandatory before a treatment with nirmatrelvir/ritonavir
can be initiated.