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\begin{document}

\title{Anticancer drugs and COVID-19 antiviral treatments in cancer patients:
what can we safely use?}



\author[1]{Paul Gougis}%
\author[1]{Charlotte Fenioux}%
\author[2]{Christian Funck-Brentano}%
\author[3]{Marianne Veyri}%
\author[4]{Joseph Gligorov}%
\author[5]{Caroline  Solas}%
\author[3]{Jean-Philippe Spano}%
\affil[1]{Hopital Pitie-Salpetriere Service de Pharmacologie}%
\affil[2]{Affiliation not available}%
\affil[3]{Pitié Salpêtrière University Hospital Department of Oncology Radiotherapy}%
\affil[4]{Sorbonne Universite}%
\affil[5]{AP-HM, Hôpital La Timone}%


\vspace{-1em}



  
  \date{May 08, 2024}


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\par\null

To the editor,

The rapid emergence of COVID-19 pandemics worldwide is of particular
concern for fragile populations who are more at risk of acute
respiratory distress syndrome and death. Patients treated for malignant
hemopathy and solid cancers have a four times higher risk of
hospitalization due to influenza infection, and a ten times higher risk
of death. This fragility could be due to their age, multiple associated
comorbidities, lymphopenia, or the immunosuppressive action of a broad
spectrum of anticancer drugs.{[}1{]} Therefore, anticancer drugs should
be used carefully in this population. Without further safety data, it
might be unsafe to treat SARS-CoV-2 positive patients who have COVID-19
symptoms with anticancer drugs known to increase infections or
harvesting immunosuppressive properties. We summarized in the table
(part A) drug classes that have been reported to increase either
neutropenia or infections. Regarding patients tested positive who have
recovered from their symptoms, clinical data is missing. It is currently
not clear if cancer treatments should be stopped, and if so, the time
needed to resume it safely.

In any of these settings, clinical trials and incoming standard of care
could lead to the prescription of antiviral drugs concomitant to
non-immunosuppressive anticancer treatments. Similar to previous works
reporting interactions between HIV antiretrovirals and anticancer
drugs,{[}2{]} these two classes of medications have a narrow therapeutic
index and can have pharmacological interactions. Some of them are
substrates or interact with hepatic cytochrome P450 cytochrome
isoenzymes (CYP), particularly CYP3A4, and pharmacokinetic interactions
could lead to supra or infratherapeutic concentrations. For example,
enzalutamide, a nonsteroidal antiandrogen prescribed for prostate
cancer, is both a CYP3A4 substrate and inducer. Ritonavir, on the other
hand, is a pharmacokinetic booster of lopinavir contained in Kaletra,
which is explored as a COVID-19 treatment. Ritonavir is a substrate and
also a potent inhibitor of CYP3A4. Thus, enzalutamide and ritonavir
could interfere with each other's metabolism, decrease or increase each
other's clearance, and be responsible for severe toxicities or decreased
efficacy. Favipiravir, an anti-EBOV drug, also a candidate for the
COVID-19 treatment, is an inhibitor of CYP2C8,{[}3{]} and therefore may
increase anticancer drug metabolized through this pathway, such as
dabrafenib and enzalutamide. Furthermore, CYP3A4 induction could lead to
sustained CYP3A4 increased activity for up to 1 week after
discontinuation. Dabrafenib or enzalutamide, two CYP3A4 inducers, could
significantly decrease hydroxychloroquine concentration during the first
week of wash-out.

Among pharmacodynamic interactions, QT interval prolongation could be of
particular interest. Hydroxychloroquine, which is currently widely
prescribed as an anti-coronavirus drug, or azithromycin, are two drugs
known to prolong QT interval. Concomitant use of QT-prolonging
anticancer drugs could lead to Torsade-de-Pointes and be fatal. Caution
should be observed in this case, and electrocardiographic monitoring
should be implemented to monitor QT interval duration during combination
therapy.

Similarly, anticancer drugs could potentiate nephrotoxicity and
hepatotoxicity of antiviral treatments.

The table (part B) summarizes pharmacokinetic and pharmacodynamics
interactions between some currently tested drugs against COVID-19 and
anticancer drugs.



\textbf{Table:}

\textbf{A - Class of anticancer drugs with immunosuppressive properties}

Immunosuppressing drugs were defined as drugs associated with
significantly more infections or neutropenia compared to the control
group or placebo in trials. These drugs were excluded from part B.

\textbf{B - Summary of pharmacokinetic (PK) and pharmacodynamic (PD)
interactions of interest concerning non-immunosuppressive anticancer
drugs and potential COVID-19 treatments.}

No interaction driven by other cytochromes were found. Red arrows are
for interactions relying on clinically significant data. Orange arrows
are for interactions relying on in vitro data for pharmacokinetic
interactions. Cytochromes involved in the drug interaction were
specified. Substrates for which induction but not inhibition could lead
to significant interaction are between brackets. When the interaction
modifies the pharmacokinetics of the anticancer drug, the arrow was on
the bottom-left. Antiviral exposition prediction is on the top-right.
Red boxes are for anticancer drugs with known Torsade-de-Pointes risk
and high risk of renal and liver toxicities. Orange boxes are for
anticancer drugs prolonging QT without known Torsade-de-Pointes risk and
moderate risk for renal and liver toxicities.

Data from FDA labels {[}4{]} were retrieved for drug metabolism, QT
prolongation, and nephrotoxicity. Livertox database was used for
hepatotoxicity{[}5{]}.



\textbf{A-}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\textbf{Immunosuppressing classes of drugs} & \textbf{Cytotoxic
chemotherapy} & \textbf{Proteasome inh.} & \textbf{Histone deacetylase
inh.} & \textbf{Anti-CD20} & \textbf{PI3K-AKT-mTOR pathway
inh.}\tabularnewline
\midrule
\endhead
& \textbf{BCR-ABLi} & \textbf{FLT3i} & \textbf{MEKi} & \textbf{JAKi} &
\textbf{BTKi}\tabularnewline
& \textbf{CDK4-6i} & \textbf{PARPi} & \textbf{Multikinase inh.
(sorafenib, sunitinib or others)} & \textbf{Multikinase inh. (sorafenib,
sunitinib or others)} & \textbf{Multikinase inh. (sorafenib, sunitinib
or others)}\tabularnewline
\bottomrule
\end{longtable}

\textbf{B-}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllllll@{}}
\toprule
\begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PK interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PD interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PD interactions}\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
\textbf{PD interactions}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{HCQ/CQ}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Azithromycin}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Lopinavir/r}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Tocilizumab} \selectlanguage{greek}\textbf{Interferon-β}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Remdesivir}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Favipiravir}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{HCQ/CQ} \textbf{Azithromycin} \textbf{Favipiravir}
\textbf{Lopinavir/r}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Lopinavir/r}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Lopinavir/r} \textbf{Tocilizumab} \textbf{Remdesivir}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{cytochromes involved in interaction}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{cytochromes involved in interaction}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{cytochromes involved in interaction}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{I\textsubscript{h}3A4} \textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{I\textsubscript{h}3A4} \textbf{I\textsubscript{h}2D6}
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{I\textsubscript{d}1A2} \textbf{(S3A4)}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{I\textsubscript{h} 2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{QT}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Nephro tox}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Liver tox}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{EGFR}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Erlotinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / S1A2}\strut
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\textbf{S3A4 / S1A2}\strut
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\textbf{S3A4 / S1A2}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
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\strut
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\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
\end{minipage}\tabularnewline
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Osimertinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
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\strut
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\textbf{Cetuximab}\strut
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\strut
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\strut
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\strut
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\strut
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\strut
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\strut
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\strut
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\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
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\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Trastuzumab}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
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\strut
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\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Pertuzumab}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
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\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
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\strut
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\textbf{Lapatinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4 / S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4 / S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4 / S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
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\strut
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\textbf{VEGF}\strut
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\textbf{Bevacizumab}\strut
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\strut
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
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\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
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\strut
\end{minipage}\tabularnewline
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\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Ramucirumab}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{BRAF}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Vemurafenib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Dabrafenib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{ALK}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Crizotinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Alectinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Ceritinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{FGFR}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Erdafitinib}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Endocrine therapies}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Tamoxifen*}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 / S2D6}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 / S2D6}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{S3A4 / I\textsubscript{d}3A4 / S2D6}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Fulvestrant}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Anastrozole}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Letrozole}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Exemestane}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Abiraterone}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{h}3A4}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Enzalutamide}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{(S3A4) / I\textsubscript{d}3A4 S2C8}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{GnRH analogs}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{Immuno-therapy}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\textbf{antiPD1/PDL1}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{*Tamoxifen is a prodrug and the reported effect is on the active
metabolite endoxifen}

\textbf{CQ: chloroquine; GnRH: gonadotrophin-releasing hormone; HCQ:
hydroxychloroquine; I\textsubscript{d}: cytochrome inducer;
I\textsubscript{h}: cytochrome inhibitor; Lopinavir/r:
lopinavir/ritonavir association (KALETRA} \selectlanguage{ngerman}®\textbf{); S: substrate}

\textbf{Conflict of interest statement}

JPS: consultant: Roche, MSD, Biogaran~; adboard/symposium: MSD, Roche,
AZ, Leopharma, Mylan, Pfizer, BMS, Novartis, PFO, Myriads, Gilead,
Lilly. All remaining authors have declared no conflicts of interest.

\textbf{References}

1. Liang W, Guan W, Chen R et al. Cancer patients in SARS-CoV-2
infection: a nationwide analysis in China. Lancet Oncol. 2020;
21(3):335-337.

2. Spano J-P, Poizot-Martin I, Costagliola D et al. Non-AIDS-related
malignancies: expert consensus review and practical applications from
the multidisciplinary CANCERVIH Working Group. Ann. Oncol. Off. J. Eur.
Soc. Med. Oncol. 2016; 27(3):397--408.

3. Liverpool COVID-19 Interactions. 2020
{[}https://www.covid19-druginteractions.org/{]}.

4. Drugs@FDA: FDA-Approved Drugs. 2020
{[}https://www.accessdata.fda.gov/scripts/cder/daf/{]}.

5. LiverTox: Clinical and Research Information on Drug-Induced Liver
Injury, Bethesda (MD): National Institute of Diabetes and Digestive and
Kidney Diseases, 2012.

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