Direct Oral Anticoagulants (DOACs) - CUH


DOACs - CUH 2015
    RIVAROXABAN
Xarelto®
APIXABAN
Eliquis®
DABIGATRAN
Pradaxa®
Prevention of stroke and systemic emboli in patients with NVAF Recommended dose 20mg od 5mg bd 150mg bd
Dose reduction

15mg od in moderate renal impairment (CrCl 30-50ml/min)

2.5 mg bd, if patients have 2 of these characteristics:
  • ≥80years or
  • ≤ 60kg or
  • serum creatinine ≥133 mmol/L
110mg bd if patient >80 years or on verapamil or for the following groups based on the assessment of thromboembolic and bleeding risks:
  • 75-80 years
  • Moderate renal impairment
  • Gastritis/oesophagitis
  • Patients with ↑risk bleeding
Severe renal impairment (CrCl 15-30 ml/min)

15mg od
To be used with caution

2.4 mg bd
To be used with caution
Contraindicated
Treatment of PE or DVT Recommended dose
  • Day 1-21 : rivaroxaban 15mg bd
  • Day 22 onwards: rivaroxaban 20mg od for 3-6 months based on transient / permanent risk factors
  • Day 1-7: apixaban 10mg bd
  • Day 8 onwards: apixaban 5mg bd for 3-6 months based on transient / permanent risk factors
  • Day 1-5 therapeutic dose LMWH
  • Day 6 onwards stop LMWH, start dabigatran 150mg bd for 3-6 months based on transient / permanent risk factors
Dose reduction

Day 22 onwards 15mg od if risk for bleeding outweighs the risk of VT

  Day 6 onwards stop LMWH, start dabigatran 110mg bd as per reduced dose in patients with NVAF
Severe renal impairment (CrCl 15-30 ml/min)

Day 22 onwards 15mg od if risk for bleeding outweighs the risk of VTE and use with caution

To be used with caution Contraindicated
Prosthetic valves

Contraindicated

Contraindicated Contraindicated
Switching from NOAC to LMWH or UFH and visa versa

Can be done at the next LMWH or UFH scheduled dose and visa versa.
Not to be administered simultaneously.

Switching from warfarin to NOAC
  • Stop warfarin
  • Start rivaroxaban when INR is ≤3.0 in NVAF
  • Start rivaroxaban when INR ≤ 2.5 in PE, DVT
  • Stop warfarin
  • Start apixaban when INR <2.0
  • Stop warfarin
  • Start dabigatran when INR <2.0
Switching NOAC to warfarin

Co-administration of rivaroxaban and warfarin for at least 2 days and continue until INR ≥ 2.0

Co-administration of apixaban and warfarin for at least 2 days and continue until INR ≥2.0
  • CrCl > 50mL/min, start warfarin 3 days before discontinuing dabigatran.
  • CrCl 30-50 mL/min: start warfarin 2 days before discontinuing dabigatran
Mechanism of action

Factor Xa inhibitor

Factor Xa inhibitor Direct thrombin inhibitor
Half life

7(±2) hours

12(±2) hours 15(±2) hours
Renal excretion

33%

25% 80%
Clinical profile

Renal functions, liver functions, RBCs, Hb and platelet count

Contraindications

Hypersensitivity to the active substance. Active significant bleeding. In hepatic disease with coagulopathy and bleeding risk. In presence of lesions or conditions with risk for major bleeding. Concomitant treatment with any other anticoagulant agent (LMWH or NOAC) except when switching to warfarin

Pregnancy / breast feeding

Contraindicated

Contraindicated Contraindicated
Food effect

With food

With/without food With/without food
Swallowing difficulties

Tables can be crushed and given via NGT (unlicensed)

Tables can be crushed and given via NGT (unlicensed) Do not open capsules
Monitoring

Not required

Not required Not required
Antidotes

Not available

Not available Under clinical trial in CUH
Drug interactions (please check medicines.ie)

Strong CYP3A4 & P-gp inhibitors (e.g. azole antifungals, protease inhibitors, dronedrone) should be avoided.

Strong CYP3A4 P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarb or St. John's wort) should be avoided.

Clarithromycin: avoid in renal impairment.

Strong CYP3A4 & strong P-gp inhibitors (e.g. azole antifungals, protease inhibitors) should be avoided.
Strong CYP3A4 and strong P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarb or St. John's wort) should be avoided.
Clarithromycin: due to ↑risk of bleeding, SPC advises against concurrent use.

Strong CYP3A4 & strong P-gp inhibitors (e.g. azole antifungals, protease inhibitors) should be avoided.

Strong CYP3A4 and strong P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarb or St. John's wort) should be avoided.

Clarithromycin: SPC advises monitoring for signs of dabigatran adverse effects such as bleeding, notably in patients with mild to moderate renal impairment.



Content by Virginia Silvari, Dr Íomhar O' Sullivan 02/11/2015. Last review Dr ÍOS 22/11/18.