IC5 DOAC DDI

Question 1

DOAC protein transporter type interactions + CYP enzyme interactions

Answer 1

Apixaban

• CYP3A4 (20%)
• PGP
• BCRP

Rivaroxaban

• CYP3A4 (50%)
• PGP
• BCRP
• OATP

Dabigatran

• PGP (typically avoid use with concomitant PgP inhibitors)
• OATP (weak inhibitory effect)

Edoxaban

• PGP
• CYP3A4 (<4%)
• OATP (weak inhibitory effect)

Question 2

Which antibiotics have interaction with DOAC?

Answer 2

1. Macrolide

• Both Clarithromycin and Erythromycin are PGP inhibitors and strong CYP3A4 inhibitors
• Increase AUC of DOAC
• *Note that Azithromycin have less interaction as it has less CYP inhibitory effects, but it still has PGP inhibitory effect

2. Rifampicin

• PgP and CYP3A4 inducer
• reduces AUC of DOAC
• concomitant use with Dabi/Apix/Riva is contraindicated due to the reduced plasma levels

Question 3

Which antiarrhythmics have interaction with DOAC?

Answer 3

Amiodarone - PgP inhibitor
Diltiazem - Pgp inhibitor and weak CYP3A4 inhibition (w Apix)
Dronedarone - Pgp inhibitor and CYP3A4 inhibition
Quinidine - Pgp inhibitor
Verapamil - Pgp inhibitor and weak CYP3A4 inhibition

*Inhibitors will increase serum conc. of the DOAC

*Digoxin has no effect on DOAC levels

Question 4

Which antiseizure medications have interaction with DOAC?

Answer 4

Carbamazepine - CYP3A4 and PGP inducer

• CI w Rivaroxaban, Dabigatran, Apixaban
• Use Warfarin instead

Phenobarbital - CYP3A4 and PGP inducer

• Avoid Rivaroxaban

Phenytoin - CYP3A4 and PGP inducer

• CI w Rivaroxaban, Dabigatran, Apixaban

Valproic acid: CYP3A4 inducer, PGP inhibitor

• Avoid all DOAC

Question 5

List the common dual inhibitors of CYP3A4 and PGP

Answer 5

DUAL INHIBITORS:

PO Azoles (Itranazole, Ketoconazole, Voriconazole, Posaconazole)
Ritonavir
Clarithromycin
Cobicistat

(Incr conc. of DOAC)

Question 6

Which two DOACs should be avoided with dual inhibitors/inducers?

Answer 6

Apixaban and Rivaroxaban

Question 7

Which azoles might still be used with a DOAC?

Answer 7

ALL azoles are contraindicated with RIvaroxaban and Apixaban

Only Ketoconazole and Itraconazole may be used with Dabigatran

Question 8

Edoxaban dose should be reduced when used concomitantly with what drugs?

Answer 8

Edoxaban dose should be reduced to 30 mg daily when combined with specific P-gp inhibitors (verapamil, quinidine, dronedarone, amiodarone, azithromycin, clarithromycin, erythromycin, itraconazole, or oral ketoconazole) in patients treated for deep vein thrombosis or pulmonary embolism. No dose adjustment is recommended for patients treated for atrial fibrillation or when used with other P-gp inhibitors.

DDI (PGP inhibitors): Amiodarone, Erythromycin (Macrolides), Ketoconazole, Quinidine, Verapamil

Question 9

What are some DOAC-herb interactions that may occur?

Answer 9

St John Worts - CYP3A4 inducer

Question 10

What are some DOAC-herb interactions that may occur?

Answer 10

St John Worts - CYP3A4, PGP, BCRP inducer
Ginkgo biloba - enhance anticoagulation effect (PD effect)
Ginseng - induce/inhibit, anticoagulation effect
Ginger - anticoagulation effect
Green tea - PGP inhibition, anticoagulation effect