1. Preventing Anticoagulation Errors with Clinical Dashboards Dan Johnson, Pharm.D., BCPS August 3, 2011

2. Objectives Describe the anticoagulant dashboards Summarize the common anticoagulant drugs and their dashboard alerts Discuss future directions in anticoagulant therapy and monitoring

3. Medication Errors with Anticoagulants Significant potential for harm at normal doses Minimal room for error with anticoagulants Always read labels carefully Monitoring is critical to prevent adverse events

4. Using Clinical Dashboards What is a “dashboard” Alert values for various drugs Concurrent monitoring of target drugs Focus on “at risk” patients when we cannot follow every patient Resolve alerts and communicate information w. providers and other pharmacists

5. Anticoagulant Drugs Heparinoids – Unfractionated heparin (UFH) – Enoxaparin (Lovenox ® ) Coumarin derivatives – Warfarin (Coumadin ® ) Direct Thrombin Inhibitors – Argatroban – Lepirudin (Refludan ® ) – Bivalirudin (Angiomax ® ) – Dabigatran (Pradaxa ® ) Factor Xa Inhibitors – Fondaparinux (Arixtra ® ) – Rivaroxaban (Xarelto ® )

6. Unfractionated Heparin Indirectly inhibits thrombin by binding to antithrombin III Large molecule with significant variability Pharmacokinetics change based on dose – Half-life increases as dose increases Where does heparin come from?

7. Pig Guts!!!

8. VUH Heparin Protocols Three main protocols – Lower dose (ACS, atrial fibrillation, etc.) – Higher dose (DVT, PE, etc) – Custom Nurses manage lower and higher dose protocols on implemented floors Providers manage the custom protocol Each protocol has limitations

9. Heparin Protocol-Items ordered

10. Higher Dose Heparin Protocol

11. Enoxaparin (Lovenox) Shorter molecule of heparin – Low molecular weight heparin vs. UFH Predictable pharmacokinetics – Does not vary by dose Simple dosing Administered subcutaneously No monitoring required – Anti-Xa levels may be used in rare situations 4 hours post dose, 0.6 to 1 for q12h treatment doses

12. Concerns with Enoxaparin Adverse events similar to heparin – Bleeding – Thrombocytopenia Lack of monitoring around invasive procedures Epidural anesthesia – Black box warning Dosing in obese patients Renal dosing for CrCl<30 ml/min

13. Heparin-induced Thrombocytopenia (HIT) HIT Type 1 (HAT) – Non-immune mediated – Usually do not drop platelets < 100,000 HIT Type 2 (HITTS) – IgG antibody against heparin-PF4 complex – Onset 3-15 days after starting heparin – 50% drop in platelet count – Associated with thrombosis

14. Treatment and Diagnosis Diagnosis – ≥ 50% drop in platelets – HIT antibody test – Serotonin release assay Treatment – Remove all sources of heparin!!! – Heparin allergy – Alternative anticoagulant Direct thrombin inhibitor Fondaparinux

15. Heparin Dashboard

16. Alert Values for Heparin Platelet drop HIT positive Old PTT/no PTT CrCl< 30 ml/min Infusion >2,500 units per hour

17. Evaluating a Dashboard Alert

18. Communicating Information Forward

19. Dashboard Functionality Alerts are addressed by clinical pharmacists in each patient care area Single pharmacist each daily responsible for final sign off Clinical pharmacists & pharmacy residents have primary dashboard responsibilities

20. Warfarin (Coumadin) Oral anticoagulant drug Inhibits vitamin K dependent clotting factors – Dietary vitamin K Where does warfarin come from? – Rat poison Indicated for long term anticoagulation – Stroke prevention – DVT/PE – Mechanical heart valves

21. Good Old Warfarin Slow onset (3-5 days) Numerous drug interactions Dietary concerns (Vit. K) Unpredictable dosing Frequent monitoring Procedural bridging Complicated patient counseling Limited alternatives

22. Warfarin Monitoring Signs of bleeding – Monitor CBC Monitor INR for clinical efficacy and safety – Normal INR 1 – Therapeutic INR 2-3 for most – Bleeding risk increases as INR goes up – INR should increase by 0.2-0.3 per day – Dose changes by 10-20%

23. Warfarin Dashboard Alerts Rapid rise in INR (>0.4 in 24 hours) High INR (INR >3) Old INR/No INR

24. Warfarin Dashboard

25. Warfarin Patient Details

26. Challenges with Dashboard Monitoring Staffing – Experience – Weekend/afterhours coverage – Practice variations Developing quality alert values – Garbage in, garbage out – Alert frequency – Positive predictive value Informatics resources

27. The Future of Anticoagulation Oral direct thrombin inhibitors – Dabigatran (Pradaxa) Oral Factor Xa inhibitors – Rivaroxaban – Apixiban – Betrixaban Several potential benefits: – Less variability – Oral administration – No monitoring required

28. Dabigatran (Pradaxa) Oral, fixed dose direct thrombin inhibitor – 150 mg twice a day Predictable pharmacokinetics Quick onset, relatively short duration Limited drug interactions, no dietary concerns No monitoring required

29. Dabigatran (Pradaxa®) Oral direct thrombin inhibitor Rapid onset Short duration of action Fixed dosing No routine monitoring required Limited drug interactions No drug-food interactions

30. Concerns with Dabigatran Renal clearance – Dose adjust for CrCl <30 ml/min – 75 mg BID – Do not give if CrCl <15 ml/min Inability to monitor around invasive procedures Capsules must be swallowed whole No reversal agent Cost

31. Why Use Dabigatran? Indicated for non-valvular atrial fibrillation – Better than warfarin – Non-inferiority data in VTE Inability to achieve stable INR on warfarin Easier transition to oral anticoagulant therapy Procedural bridging may be easier Rapid onset compared to warfarin Patient must be able to afford dabigatran

32. When to Avoid Dabigatran Renal failure Indications without data for dabigatran – Mechanical heart valves – VTE prophylaxis – Heparin-induced thrombocytopenia Cost concerns with dabigatran Stable warfarin patients? Can pharmacogenomics make warfarin dosing easier/better?

33. Rivaroxaban (Xarelto) Oral factor Xa inihibitor FDA approved for ortho prophylaxis – 10 mg daily Take with or without food Substrate of CYP P450 3A4 and pGP Avoid use if CrCl <30 ml/min Half life 5-9 hours Per tube administration may reduce bioavailability

34. Rivaroxaban Dosing Ortho prophylaxis – 10 mg once daily starting 6 to 10 hours after surgery – Only FDA approval at this point DVT/PE – 15 mg BID for 3 weeks followed by 20 mg daily Atrial fibrillation – 20 mg once daily, 15 mg daily for moderate renal impairment

35. Future Directions Improve dashboard functionality – New alerts (old drugs and new) – Newer monitoring systems (Sentri7) Utilize new anticoagulants in appropriate patients Clinical pharmacist focusing on only anticoagulation Inpatient anticoagulation service

36. Questions?