[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19. / Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the. inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Assessment of the effectiveness of tocilizumab on mortality and progression to mechanical ventilation or intensive care in patients with COVID-19 admitted to a tertiary hospital.

OBJECTIVES: The evidence for tocilizumab in the treatment of COVID-19 is contradictory, with some clinical trials showing benefits in regard to progression to mechanical ventilation (MV) and/or mortality. The aim of this study is to evaluate in real clinical practice the effectiveness of tocilizumab in treating COVID-19 and to identify prognostic factors for patient outcomes. METHODS: This was an observational, retrospective study of COVID-19 patients treated with tocilizumab between March 2020 and February 2021 in a tertiary hospital. Variables were demographics, comorbidities, vital signs, analytical parameters, COVID-19 treatment, progression to MV, intensive care unit (ICU) admission, hospital stay, and mortality. RESULTS: A total of 685 patients (64.7% men, median 68 years) were included. Overall mortality was 23.4% (14.2% in the first 14 days post-tocilizumab) and 93.3% in patients with MV and/or in the ICU at 14 days post-tocilizumab. In addition, 61.5% of discharges occurred during the same period. In patients who died, statistically significant differences were observed in the baseline analytical parameters of C-reactive protein (CRP), D-dimer and higher lactate dehydrogenase (LDH) (p<0.05). CONCLUSIONS: In most patients the clinical results of tocilizumab were observed at 14 days post-administration and could benefit from earlier administration of treatment. Baseline levels of CRP, D-dimer and LDH could be prognostic factors for the evolution of the COVID-19 patient.