DOAC - Indication & Doses

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Why this page is important: The dose for a DOAC depends on the condition you are treating or preventing. Remember; DOACs are only licensed for stroke reduction in AF & for the treatment of VTE & PE.   You can also refer to this page when assessing a patient for suitability to switch from warfarin to a DOAC.

Stroke risk reduction in Atrial Fibrillation 

 
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Standard dose

 5mg bd

150mg bd 60mg od 20mg od
Dose amendments

Reduce dose to 2.5mg twice daily if two or more of the following

  • creatinine > 133umol/l 
  • age > 80 years
  • weight < 60kg

Reduce dose to 2.5mg twice a day if CrCl is between 15-29 ml/minute

CrCl <15 DOAC contraindicated

ALT/AST >2 x ULN or total bilirubin ≥1.5 x ULN) apixaban should be used with caution (these patients were excluded from clinical trials)

Reduce dose to 110mg twice a day if any of the following

  • age >80 years

  • taking verapamil 

Consider reducing dose to 110mg twice a day if any of the following

  • CrCl 30-50 ml/minute
    age 75-80 years
  • there are clinical risk factors for bleeding
  • gastritis, oesophagitis or GORD

CrCl <15 DOAC contraindicated

LFTs are > 2x the upper limit of normal - the SPC for dabigatran states that there is no evidence to support use– therefore suggest that review treatment with specialist input if needed

Reduce dose to 30mg once a day if any of the following

  • CrCl is 15-50 ml/minute
  • body weight  60kg
  • concomitant use of ciclosporin, dronedarone, erythromycin or ketoconazole 

CrCl <15 DOAC contraindicated

ALT/AST > 2 x ULN or total bilirubin ≥ 1.5 x ULN - edoxaban should be used with caution (these patients were excluded from clinical trials)

Reduce dose to 15mg once a day if CrCl is 15-49 ml/minute  

CrCl <15 DOAC contraindicated

Treatment of Venous Thromboembolism (DVT and PE) 

  Apixaban Dabigatran Edoxaban Rivaroxaban
Standard dose 10mg bd for the first 7 days then reduce dose to 5mg bd  150mg bd (followed by parenteral anticoagulant for at least 5 days 60mg once a day ( following treatment with parenteral anticoagulant for at least 5 days) 15mg twice a day for 3 weeks ( 21 days) then reduce dose to 20mg once a day thereafter) 
 Dose amendments

The manufacturers do not give any specific dosing reduction recommendations in renal impairment but advise caution if the CrCl is less than 30 ml/minute

A lower dose of 2.5mg twice a day may be considered for the prevention of recurrent DVT and/or PE after at least 6 months at above treatment dose

ALT/AST >2 x ULN or total bilirubin ≥1.5 x ULN) apixaban should be used with caution (these patients were excluded from clinical trials)

 Reduce dose to 110mg twice a day if any of the following

  • age >80 years
  • taking verapamil

Consider reducing dose to 110mg twice a day if any of the following

  • CrCl 30-50 ml/minute
  • age 75-80 years
  • there are clinical risk factors for bleeding 
  • gastritis, oesophagitis or GORD 

LFTs are > 2x the upper limit of normal - the SPC for dabigatran states that there is no evidence to support use– therefore suggest that review treatment with specialist input if needed.

Reduce dose to 30mg once a day if any of the following

  • CrCl is 15-50 ml/minutebody

  • weight < 60kg

  • concomitant use of ciclosporin, dronedarone, erythromycin or ketoconazole

ALT/AST > 2 x ULN or total bilirubin ≥ 1.5 x ULN - edoxaban should be used with caution (these patients were excluded from clinical trials)

Consider a dose reduction from 20mg once a day to 15mg once a day if high bleeding risk

A lower dose of 10mg once a day may be considered for the prevention of recurrent DVT and/or PE after at least 6 months at above treatment dose

 Antiphospholipid syndrome 

 
  • DOACs are not recommended in these patients
  • There is not enough evidence that any DOAC offers sufficient protection in patients diagnosed with established antiphospholipid syndrome, particularly in patients at the highest risk for thromboembolic events (those who test positive for all 3 antiphospholipid tests – lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies)
  • These patients need to take warfarin

 Mechanical mitral or aortic prosthetic heart valves

 
  • DOACs are NOT licensed for patients with mechanical valves
  • Evidence is mounting that dabigatran is associated with mechanical valve thrombosis. Therefore, patients with mechanical heart valves, regardless of position (mitral or aortic), should not be treated with dabigatran as a replacement for warfarin

Seek specialist advice for

  • Extremes of bodyweight < 50kg or > 120kg
    • When calculating CrCl for these patients in primary care: adjusted BW for >120kg and actual BW for ​<50kg ​
  • Heart failure patients with fluid overload- use dry weight/ euvolaemic estimate
  • CrCl <15 - DOAC contraindicated
  • Patients with extensive amputations, or neurological diseases (eg spina bifida, multiple sclerosis) and myopathy that may result in profound muscle loss

HASBLED

More than >3 : patient is at a high risk of bleeding and apixaban should be used cautiously, with regular reviews

 

https://www.ahajournals.org/doi/pdf/10.1161/JAHA.115.002776 

https://www.gov.uk/drug-safety-update/direct-acting-oral-anticoagulants-doacs-increased-risk-of-recurrent-thrombotic-events-in-patients-with-antiphospholipid-syndrome

 

apixaban dabigatran edoxaban rivaroxaban

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