IC5- DOACs DDIs

Question 1

What are the 5 types of drugs that DOACs have DDIs with?

Answer 1

1. Macrolides
2. Rifampicin
3. Anti-seizure medications
4. Herbal
5. Azole antifungals

Question 2

How does macrolides cause DDI with DOACs?

How should we correct the dosing?

Answer 2

• P-gp inhibition and strong CYP3A4 inhibition → accumulation of DOACs
• Decrease dose of DOACs

Question 3

Elaborate on the DDI of rifampicin with DOACs.

Is there need for alternative Tx? If yes, what is it?

Answer 3

• P-gp/BCRP and CYP3A4 induction → 🚫C/I with ALL DOAC use
• Hence if pt is alr on Rifampicin and needs a drug for SPAF, use warfarin
  When swapping to warfarin, ALWAYS consider genotyping

(Extra)
- DOAC → warfarin, no need to hold off DOAC, can just immediately start on warfarin while you continue DOAC (if edoxaban, half dose). Wait for 2-3 days, then take INR again. If INR < 2, continue DOAC intake (if edoxaban, half dose) and repeat INR after 1-3 days (before DOAC intake). But if INR > 2, discontinue DOAC and repeat INR 1 day after stopping.
- But switching from warfarin to DOAC → hold off warfarin for 3 days + INR < 2 then start DOAC

Question 4

Which antiseizure medication is Dabigatran etexilate C/I with?

Answer 4

Carbamazepine, phenytoin, valproic acid

Question 5

Which antiseizure medication is Apixaban C/I with?

Answer 5

Valproic acid

Question 6

Which antiseizure medication is Edoxaban C/I with?

Answer 6

Valproic acid

Question 7

Which antiseizure medication is Rivaroxaban C/I with?

Answer 7

Carbamazepine, phenobarbital, phenytoin, valproic acid

Question 8

Elaborate on the DDI of herbal medications (St John’s Wort) with DOACs

Answer 8

• Dabigatran etexilate and rivaroxaban: 🚫C/I with St. John’s Wort (very potent CYP3A4 and P-gp inducer)
• Apixaban and edoxaban: use with ⚠️CAUTION

Question 9

Elaborate on the DDI of azole antifungals with DOACs

Answer 9

• Rivaroxaban and apixaban: 🚫 C/I with azole antifungals
• Dabigatran: 🚫 C/I with azole antifungals (except keto/ itraconazole)