Discussion
This is the first study assessing severe DDI pairs of LPV/RTV used in
the treatment of COVID-19 patients and were predicted to cause
clinically significant life-threatening ADRs.
The findings of this study have great novelty in terms of reducing
clinician burdens especially when DDI alert fatigues may expected to
occur in this emergency pandemic health situations. This study has
tabulated the composite lists of severe DDI pairs of LPV/RTV that were
recognized by both the international well-recognized evidenced-based
resources and is highly recommended to check at least 10 severe DDI
pairs of LPV/RTV to reduce the risk of life-threatening ADRs.
Meanwhile, it is also noteworthy that in many developing countries,
computer based DDI alert systems may not available and clinicians in
these countries may be advantaged greatly from the severe DDI pairs
identified in this study in general, and in particular the composite
list recognized by both the international drug interactions resources.
Important findings of this study revealed that clinicians should not
depend on any particular DDI checking systems of LPV/RTV and may be
other COVID-19 drugs as well since high level of discrepancies were
identified in this study. For example, if clinicians solely rely on the
Liverpool COVID-19 DDI checking system which has recently emerged
specifically for COVID-19 therapeutics, it is found that around seven
very clinically important drugs may be missed for checking DDIs that may
cause life-threatening ADRs. On the other hand, if clinicians solely
rely on the FDA prescribing information of LPV/RTV, it is found that
around 45 very clinically important drugs may be missed for checking
DDIs that may also cause life-threatening ADRs. Therefore, it is
suggested to undertake systematic cross-comparison in future by the
professional DDI bodies to reduce disagreement in between the drug
interaction resources. Also, suggested to identify any discrepancies by
the clinicians in order to avoid missing any interacting drugs predicted
to cause clinically significant DDIs.
It is important to recognize that
although different other ways e.g. computerized DDI alerts12,13, web-based DDI checkers etc. can be used to
identify potential clinically significant DDIs of LPV/RTV, however there
are lots of limitations of these checking systems including alert
fatigues 11, lack of robust evidence of the
interactions etc. The findings of the present study may therefore serve
as considerably best severe DDI pairs of LPV/RTV predicted to cause
life-threatening ADRs since the DDI pairs were identified from the
internationally well-recognized evidenced based DDI resources.