NOACs
NOACs can directly inhibit thrombin (dabigatran) or factor Xa
(rivaroxaban, apixaban and edoxaban) and are prescribed more commonly
for stroke prevention in AF.52NOACs have been
recommended as the first-line medications unless contraindications are
present.36Different from warfarin, NOACs have less
drug-drug or drug-food interactions and are prescribed at a fixed dose
following individual dosage criteria without routine monitorof the drug
concentrations or anticoagulation
activities.53However, NOACs still have drug-drug
interactions with some medications. An important interaction mechanism
for all NOACs is significant gastrointestinal re-secretion over a P-gp
transporter after absorption in the gut. Competitive inhibition of this
pathway will result in increased plasma
levels.53Besides, CYP3A4-dependent elimination is
relevantly involved in the hepatic clearance of rivaroxaban and
apixaban. Strong CYP3A4 inhibition or induction may affect plasma
concentrations.53Based on these concepts, COVID-19
medications which could compete or inhibit P-gp or CYP3A4 would result
in increased plasma levels of NOACs.
As Table 2 shows, HCLQ is a substrate of CYP3A4, and therefore, may
pontentially increase the plasma concentrations of NOACs. Generally,
NOACs could be co-administered with HCLQ with either usual dosages
(apixaban or rivaroxaban) or dosage adjustments (dabigatran or
edoxaban). However, marcolides (e.x. erythromycin or clarithromycin or
azithromycin) are moderate P-gp competitors and strong CYP3A4
inhibitors, and may increase the exposures of NOACs by 15-20% for
dabigatran, 60% for apixaban, 90% for edoxaban and 34%
(erythromycin)/54% (clarithromycin) for
rivaroxaban.53Therefore, if HCLQ plus azithromycin
regimen is adopted to AF patients with COVID-19 , the NOACs should be
co-administered with cautions.
Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA
polymerases, provides a great hope for the treatment of COVID-19
infection.9Remdesivir is expected to have no
significant effects on the metabolisms or eliminations of all four
NOACs, and could be co-administrated with NOACs.