Crushing lopinavir-ritonavir tablets may decrease the efficacy of therapy in COVID-19 patients

With the recent COVID-19 pandemic, there are multiple proposed therapies including remdesivir, hydroxychloroquine, and lopinavir-ritonavir [1]. In a recent study, Cao et al. compared lopinavir-ritonavir tablets to placebo for treatment of severe COVID-19 and did not find a clear benefit [2]. The study protocol used crushed tablets to prepare suspensions in patients who were unable to swallow. In the lopinavir-ritonavir group, crushed tablets are expected to have been received by at least 14.1% of patients who received invasive mechanical ventilation. However, crushing tablets is not recommended by the drug manufacturers [3]. In addition, a randomized, open-label, cross-over study of children found the area under the concentration versus time curve (AUC) was significantly reduced with crushed lopinavir-ritonavir tablets versus intact tablets [4]. The reduction in AUC was 45% for lopinavir and 47% for ritonavir. Considering these data, crushing tablets in the Cao et al. study might have had lowered the measured efficacy of lopinavir-ritonavir. Therefore, it would be important to know the exact percentage of patients who received the crushed tablets and to conduct a post-hoc analysis of the treatment efficacy in patients who received intact tablets, crushed tablets in relation to placebo. There are several key research questions that need to be answered, such as the optimal dosage of lopinavir-ritonavir, the pharmacokinetic characteristics in mild or severe COVID-19 patients. In future lopinavir-ritonavir clinical trials, patients on invasive mechanical ventilation would benefit from the use of oral solution of this medication [2]. If not available, increasing the dose might be considered. However, it is also important to note that lopinavir-ritonavir solution is not recommended for use with polyurethane feeding tubes due to potential incompatibility. Lopinavir-ritonavir solution could be used with silicone or polyvinyl chloride (PVC) feeding tubes [3].