1. Non-vitamin K antagonist oral anticoagulants (NOACs) YOUR FACILITY Presenter Month YYYY September 2016 Version 2

2. This session will provide an: Introduction to high-risk medicines Overview of NOACs (also known as ‘DOACs’ – Direct Oral Anticoagulant), including: – NOACs available – Indications Version 2 – Contraindications – Adverse effects – Prescribing, administering and supply – Specific NOAC risks 2 September 2016 Version 2

3. ‘A-PINCH’ A – Anti-infectives P – Potassium & other concentrated electrolytes I – Insulins N – Narcotics and other sedatives C – Cytotoxic agents H – Heparins and other anticoagulants 3 September 2016 Version 2

4. Features of High-Risk Medicines: More likely to cause harm if involved in an error Narrow therapeutic window Multiple interactions with other medications Potent medications Complex dosage and monitoring schedules Wide variation in effect 4 September 2016 Version 2

5. Anticoagulant medicines: Are used extensively in clinical practice Act through targeting a number of different proteins that may limit or prevent thrombus formation Have a narrow therapeutic index and over or under anticoagulation can result in significant adverse patient outcomes Choice of anticoagulant will be based on a variety of patient factors and indication for treatment Until introduction of NOACs, warfarin was the only oral anticoagulant available 5 September 2016 Version 2

6. There are currently three NOACs registered in Australia: One direct thrombin inhibitor: Dabigatran (Pradaxa®) 6 September 2016 Version 2

7. Two Factor Xa inhibitors: Apixaban (Eliquis®) Rivaroxaban (Xarelto®) 7 September 2016 Version 2

8. NOAC indications include: Reduces risk of stroke in non-valvular atrial fibrillation Prevention of VTE following hip or knee replacement Treatment and ongoing prevention of VTE 8 September 2016 Version 2

9. Contraindications to NOAC therapy include: Renal impairment – a reduced dose may be used in moderate renal impairment, depending on renal function, NOAC and indication Disorders of haemostasis Clinically significant active bleeding Prosthetic heart valve Liver disease Pregnant and breastfeeding women Children under 18 years 9 September 2016 Version 2

10. NOAC adverse effects 10 DabigatranApixabanRivaroxaban Commonbleeding anaemia nausea dyspepsia gastritis abdominal pain bleeding anaemia dyspepsia GI bleeding bleeding anaemia peripheral oedema itch, skin blisters muscle spasm Infrequentincreased liver enzymes thrombocytopenia increased liver enzymes Rareallergic reactions September 2016 Version 2

11. Dabigatran reversal with Idarucizumab: Idarucizumab (Praxbind®) is used to reverse the anticoagulant effects of dabigatran It is indicated when rapid reversal of dabigatran is required: – for emergency surgery/urgent procedures – in life-threatening or uncontrolled bleeding Idarucizumab may not be available in all facilities Reversal agents for apixaban and rivaroxaban are currently not available. 11 September 2016 Version 2

12. NOAC dosing Unlike warfarin: NOAC doses are fixed based upon patient factors, such as renal function and indication of therapy Dose frequency is either daily, or twice daily depending on indication Duration of therapy is dependent on the indication for therapy 12 September 2016 Version 2

13. NOAC monitoring Unlike warfarin: There is no need to routinely measure patient blood levels and make dose adjustments according to a ‘therapeutic range’ However: NOACs are excreted renally. Renal function should be monitored: – at least annually – if the patients condition changes Patients should also be routinely assessed for signs of bleeding and for other bleeding risk factors (e.g. persistent hypotension; other medicines; platelet counts) 13 September 2016 Version 2

14. Prescribing NOACs on the National Inpatient Medication Chart (NIMC) Check all charts in case an anticoagulant medicine has already been ordered The NOAC should be prescribed in either a ‘Regular Medication’ order space, or following VTE risk assessment, on the ‘VTE prophylaxis section’ 14 NIMC Regular medicine order space NIMC VTE prophylaxis section September 2016 Version 2

15. Prescribing therapeutic dose NOACs on the NIMC Use a NIMC ‘regular medicine’ order space Include the ‘Indication’ in the order: – allows the medicine to be reviewed in terms of why it was ordered – reduces the risk of misinterpretation of the order e.g. medicines with look-a-like names or incorrect doses and for medicines which have different doses for different indications 15 September 2016 Version 2

16. Prescribing VTE prophylaxis dose NOACs on the NIMC Use the NIMC VTE prophylaxis section The ‘Indication’ is preprinted in this section If VTE therapy is required e.g. for a pre-existing DVT, it should be charted in a regular medicines order space 16 September 2016 Version 2

17. Documenting NOAC education on the NIMC NOAC education can be documented on the NIMC in the ‘Warfarin Education Section’ Warfarin should be crossed out and the name of the NOAC inserted. 17 September 2016 Version 2

18. NOAC administration instructions: Dabigatran (Pradaxa ® )  Swallow whole with or without food  Do not chew or open capsule  Keep in original packaging  Do not transfer capsule to a dose administration aid Apixaban (Eliquis ® )  Swallow whole with or without food  Can be used in dose administration aids Rivaroxaban (Xarelto ® )  10 mg tablet may be taken with or without food  15 mg and 20 mg tablet should be taken with food  Can be used in dose administration aids 18 Images courtesy of MIMS Australia September 2016 Version 2

19. Accessing NOAC supplies NOACs are short-acting medicines. Dose omission may put the patient at risk of thrombosis Inform the ward pharmacist when a patient is admitted or commenced on a NOAC If the prescribed NOAC is not available as imprest supply, and the Pharmacy Department, is closed the NOAC should be sourced by: – Contacting the After-Hours Pharmacist – Sourcing it through the After-Hours Supply Contact the relevant medical officer if a dose is still not available The chart shouldn’t simply be marked as ‘N’ (not available) 19 September 2016 Version 2

20. General NOAC safety considerations: For all patients receiving anticoagulants clinicians should be alert to signs of bleeding Patients taking anticoagulants are at increased risk of bleeding if they fall (refer to local fall protocol) All patients (and/ or their carer) receiving or going home on an anticoagulant require education on their medicines 20 September 2016 Version 2

21. Specific NOAC risks Specific incidents that have been identified associated with NOAC use: Failure to recognise these medicines as anticoagulants – For example, venous thromboembolism (VTE) prophylaxis (enoxaparin) prescribed along with a NOAC Anticoagulants prescribed on different charts – Intravenous heparin is prescribed on an IV heparin chart and a NOAC is prescribed on the NIMC 21 September 2016 Version 2

22. Specific NOAC risks Failure to realise clinical significance of NOACs – For example, doses omitted and documented ‘N’ (not available) – If there is any doubt whether a dose has been given, contact the medical officer, don’t simply omit Mismanaged during the perioperative period – For example, the NOAC is ceased too early prior to a procedure Risk of drug interactions – Specific interactions and medicines that increase bleeding risk 22 September 2016 Version 2

23. In summary: NOACs (anticoagulants) are a high-risk medicine As with all medicines, if the patient’s condition changes NOAC use may need to be reviewed NOACs need to be sourced, or the medical officer notified if not available For all anticoagulants, check that duplicate anticoagulant therapy hasn’t inadvertently been prescribed 23 September 2016 Version 2

24. References 24 Australian Commission on Safety and Quality in Health Care. NIMC User Guide. 2014. http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03072-3. http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03072-3. Bayer Australia LTD. Xarelto® (Rivaroxaban) Product Information. Registered Trademark of Bayer AG Therapeutic Goods Administration Website 2016 [updated 1 June 2016]; Available from: www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01020-3. www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01020-3. Boehringer Ingelheim Pty Limited. Product Information Pradaxa® (dabigatran etexilate). Therapeutic Goods Administration Website 2015 [updated 10 June 2016]; Available from: http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01177-3 http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01177-3 Boehringer Ingelheim Pty Limited. Product Information Praxbind® (idarucizumab). Therapeutic Goods Administration Website 2016. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-01849-1 https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-01849-1 Bristol-Myers Squibb Australia Pty Ltd. Product Information Eliquis® (apixaban) Therapeutic Goods Administration Website2015 [updated 2 October 2015]; Available from: http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03072-3. http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03072-3. September 2016 Version 2

25. Policy and resources: 25 Australian Commission on Quality and Safety in Health Care, NIMC User Guide www.safetyandquality.gov.au/publications/nimc-user-guid/ www.safetyandquality.gov.au/publications/nimc-user-guid/ Government of Western Australia. Living with a New Oral Anticoagulant (NOAC) www.watag.org.au/wamsg/docs/Living_with_a_NOAC_2015.pdf www.watag.org.au/wamsg/docs/Living_with_a_NOAC_2015.pdf NSW Clinical Excellence Commission NOAC Guidelines www.cec.health.nsw.gov.au/programs/high-risk-medicines/anticoagulants#noac NSW Health Policy on High-Risk Medicine Management www0.health.nsw.gov.au/policies/pd/2015/PD2015_029.html www0.health.nsw.gov.au/policies/pd/2015/PD2015_029.html National Prescribing Service (NPS) www.nps.org.au/medicines/heart-blood-and-blood-vessels September 2016 Version 2

26. Thank you Questions 26 For further information: CEC-MedicationSafety@health.nsw.gov.au www.cec.health.nsw.gov.au September 2016 Version 2