NOAC indications and PBS listings

Three non-vitamin K antagonist oral anticoagulants (NOACs) are approved for use in Australia: apixaban (Eliquis), dabigatran (Pradaxa) and rivaroxaban (Xarelto).1-3

They are all listed on the PBS general schedule as Authority Required (STREAMLINED). They can be prescribed by medical practitioners and nurse practitioners.4-6

A summary of approved NOAC indications and PBS listings is provided below. Before prescribing through the PBS, please confirm clinical and treatment criteria. View the TGA approved Product Information (PI) and go to the PBS website for complete details.

 

NOAC TGA-approved indications and PBS listings

Prevention of stroke and systemic embolism (SE) in adults with non-valvular atrial fibrillation (NVAF) and at least one additional risk factor for stroke

Apixaban, dabigatran and rivaroxaban are all PBS listed for the prevention of stroke and SE in adults with NVAF and at least one additional risk factor for stroke (see Table 1).4-6

Table 1: NOAC dosing and PBS listings for prevention of stroke and SE in patients with NVAF

RecommendationApixaban1,4Dabigatran2,5Rivaroxaban3,6
Dosing   
5 mg twice daily150 mg twice daily20 mg once daily
Dose adjustments2.5 mg twice daily for patients with ≥ 2 of:
  • age ≥ 80 years
  • body weight ≤ 60 kg
  • serum creatinine ≥ 133 µmol/L
110 mg twice daily in patients with any of:
  • age ≥ 75 years
  • CrCl 30–50 mL/min
  • high risk of major bleeding
15 mg once daily in patients with CrCl 30–49 mL/min

15 mg once daily in patients with CrCl 15-29 mL/min 
(Use with caution)
PBS listed
YesYesYes

Table 1 abbreviations: CrCl, creatinine clearance.

Prevention of venous thromboembolism (VTE) events in adults who have undergone elective total hip or total knee replacement surgery

Apixaban, dabigatran and rivaroxaban are all PBS-listed for the prevention of VTE events in adults who have undergone elective total hip or knee replacement surgery (see Table 2).4-6

Table 2. NOAC dosing and PBS listings for VTE prevention following hip/knee replacement surgery

RecommendationApixaban1,4Dabigatran2,5Rivaroxaban3,6
Dosing   
2.5 mg twice daily for 32–38 days (hip) or 10–14 days (knee)220 mg once daily for 28–35 days (hip) or 10 days (knee)10 mg once daily for 35 days (hip) or 14 days (knee)
Dose adjustmentsNot stated in PI
150 mg once daily in patients with CrCl 30–50 mL/min
Not stated in PI
PBS listed
YesYesYes

Table 2 abbreviations: CrCl, creatinine clearance; PI, TGA-approved product information.

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), or prevention of recurrent DVT and PE in adults

Apixaban and rivaroxaban, but not dabigatran, are PBS listed for the treatment of DVT and PE, or prevention of recurrent DVT and PE in adults (see Table 3).4-6

Table 3: NOAC dosing and PBS listings for treatment or prevention of DVT and PE

RecommendationApixaban1,4Dabigatran2,5Rivaroxaban3,6
Dosing   
Treatment: 10 mg twice daily for 7 days, then 5 mg twice daily


Prevention: 2.5 mg twice daily, after ≥ 6 months of DVT/PE treatment

150 mg twice daily, following treatment with a parenteral anticoagulant for ≥ 5 daysTreatment: 15 mg twice daily for 21 days


Prevention: 20 mg once daily, after 21 days of DVT/PE treatment.

Consider 10 mg once daily after 6-12 months of DVT/PE treatment based on individual assessment of risk of recurrence vs bleeding risk 

Dose adjustmentsNot stated in PI
110 mg twice daily in patients with any of:
  • age ≥ 75 years
  • CrCl 30–50 mL/min
  • high risk of major bleeding 
Not stated in PI
PBS listed
YesNoYes

Table 3 abbreviations: CrCl, creatinine clearance; DVT, deep vein thrombosis; PE, pulmonary embolism; PI, TGA-approved product information.

Prevention of major cardiovascular events (composite of stroke, myocardial infarction and cardiovascular death) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD)

Rivaroxaban is PBS listed for the prevention of major cardiovascular events (composite of stroke, myocardial infarction and cardiovascular death) in patients with CAD and/or PAD when used in combination with aspirin.3*

Table 4. Rivaroxaban dosing and PBS listing for prevention of major cardiovascular events in CAD and/or PAD

Recommendation

Rivaroxaban3,8

Dosing

Rivaroxaban 2.5 mg twice daily in combination with 100 mg aspirin daily

Dose adjustments

Not stated in PI

PBS listed

Yes

* but no other anti-platelet therapy

 

Supporting information

Risk factors for developing stroke

Risk factors for developing stroke or SE (ischaemic) specified by the PBS are listed below. They are the same for apixaban, dabigatran and rivaroxaban.4-6

  • Prior stroke (ischaemic or unknown type), transient ischaemic attack or non-central nervous system SE
  • Age ≥ 75 years
  • Hypertension
  • Diabetes mellitus
  • Heart failure and/or left ventricular ejection fraction ≤ 35%

NOAC contraindications

Rrenal, hepatic and bleed-related contraindications, as well as contraindicated concomitant medicines, are summarised below (see Table 5).

Table 5: Contraindications listed in the NOAC product information sheets

ContraindicationApixaban1Dabigatran2Rivaroxaban3
Renal   
CrCl < 25 mL/min
CrCl < 30 mL/minUndergoing dialysis

CrCl < 30 mL/min
(15 mg and 20 mg tablets)

CrCl < 15 mL/min
(10 mg tablets)

HepaticHepatic disease associated with coagulopathy and clinically relevant bleeding risk, including severe hepatic impairment (Child-Pugh C)
Hepatic impairment or liver disease expected to have any impact on survival

Manufacturer also contraindicates use if liver enzymes > 2 x ULN

Significant hepatic disease (including Child-Pugh B and C), which is associated with coagulopathy leading to a clinically relevant bleeding risk
Bleed-relatedSpontaneous or pharmacological impairment of haemostasis

Clinically significant active bleeding

Lesion or condition at significant risk of major bleeding		Haemorrhagic manifestations, bleeding diathesis, or spontaneous or pharmacological impairment of haemostasis

Lesion or condition, if considered a significant risk factor for major bleeding

History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding

GI haemorrhage within the past year unless the cause has been permanently eliminated

Conditions associated with increased risk of bleeding		Clinically significant active bleeding

Lesions at increased risk of clinically significant spontaneous impairment of haemostasis

Concomitant medicines
Strong inhibitors of both CYP3A4 and P-gp (eg, ketoconazole, ritonavir)

Other anticoagulants		Systemic ketoconazole, ciclosporin, itraconazole

Other anticoagulants		Strong inhibitors of both CYP3A4 and P-gp (eg, azole antifungals, ritonavir)

Other anticoagulants not recommended (precaution)

Table 5 abbreviations: CrCl, creatinine clearance; CYP, cytochrome P450; GI, gastrointestinal; P-gp, P-glycoprotein; ULN, upper limit of normal.

 

References

  1. Bristol-Myers Squibb Australia Pty Ltd. Apixaban (Eliquis) product information (accessed 19 October 2020).
  2. Boehringer Ingelheim Pty Limited. Dabigatran etexilate (Pradaxa) product information (accessed 19 October 2020).
  3. Bayer Australia Ltd. Rivaroxaban (Xarelto) product information (accessed 19 October 2020).
  4. Australian Government Department of Health. PBS Schedule. Apixaban. 2017 (accessed 19 October 2020).
  5. Australian Government Department of Health. PBS Schedule. Dabigatran. 2017 (accessed 19 October 2020).
  6. Australian Government Department of Health. PBS Schedule. Rivaroxaban. 2017 (accessed 19 October 2020).
  7. Pharmaceutical Benefits Scheme. Public Summary Document: Rivaroxaban (March 2019). Canberra: Australian Government Department of Health, 2019