The (Hopefully) Bloodless Battle for Safe Use of DOACs. Gale E. Garmong, PharmD Clinical/Staff Pharmacist Klingensmith s Drug Stores

Transcription

1 The (Hopefully) Bloodless Battle for Safe Use of DOACs Gale E. Garmong, PharmD Clinical/Staff Pharmacist Klingensmith s Drug Stores

2 Objectives At the completion of this activity, the participant will be able to Discuss the role of direct oral anticoagulants (DOACs) in anticoagulation, including agents FDA-approved indications and place within guidelines. Recommend appropriate dosing (or possibly avoidance) of specific DOACs based on indication and patient-specific factors, including drug interactions. Formulate a monitoring plan for patients on DOACs.

3 Objectives At the completion of this activity, the participant will be able to Discuss the role of direct oral anticoagulants (DOACs) in anticoagulation, including agents FDA-approved indications and place within guidelines. Recommend appropriate dosing (or possibly avoidance) of specific DOACs based on indication and patient-specific factors, including drug interactions. Formulate a monitoring plan for patients on DOACs.

4 Coagulation Cascade Front. Cell. and Infect. Microbiol Sept 11;4: Sept.

5 FDA Approvals 1954 Warfarin (COUMADIN) Vit K Antagonist (VKA) Inhibits C1 subunit of Vitamin K epoxide reductase (VKORC1) Prevents regeneration of active Vit K for clotting factor synthesis Drug/food interactions & pharmacogenomic considerations variable dosing needs oexogenous vitamin K oprotein binding ocyp2c9 (also 1A2, 3A4, 2C19, 2C8, 2C18) interactions/variants ovkorc1 variants Need to monitor INR Initial pro-coagulant effect d/t inhibition of Protein C & S Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2017.

6 Warfarin (VKA) Adapted from: Front. Cell. and Infect. Microbiol Sept 11;4: Sept.

7 FDA Approvals 1954 Warfarin (COUMADIN) 2010 Dabigatran (PRADAXA) Direct thrombin inhibitor (DTI) Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim; 2018.

8 Direct Thrombin Inhibitor (DTI) Adapted from: Front. Cell. and Infect. Microbiol Sept 11;4: Sept.

9 FDA Approvals 1954 Warfarin (COUMADIN) 2010 Dabigatran (PRADAXA) 2011 Rivaroxaban (XARELTO) 2012 Apixaban (ELIQUIS) 2015 Edoxaban (SAVAYSA) 2017 Betrixaban (BEVYXXA) Factor Xa inhibitors

10 Factor Xa Inhibitors Adapted from: Front. Cell. and Infect. Microbiol Sept 11;4:128.

11 Direct Oral Anticoagulants (DOACs) 1954 Warfarin (COUMADIN) 2010 Dabigatran (PRADAXA) 2011 Rivaroxaban (XARELTO) 2012 Apixaban (ELIQUIS) 2015 Edoxaban (SAVAYSA) 2017 Betrixaban (BEVYXXA) DOACs / Target Specific Oral Anticoagulants (TSOACs) / Novel (or Non-vitamin K) Oral Anticoagulants (NOACs not to be confused with no anticoagulation ) NOAC, DOAC, or TSOAC Pharmacy Times Sept 19.

12 FDA Approved Indications/STANDARD Dosing Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation (AF) Treatment of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) Reduction in the risk of recurrence of DVT and/or PE Dabigatran (PRADAXA) 1 Rivaroxaban (XARELTO) 2 Apixaban (ELIQUIS) 3 Edoxaban (SAVAYSA) 4 Betrixaban (BEVYXXA) mg BID 150 mg BID (p 5-10 d. of parenteral AC) 20 mg daily w/ evening meal 15 mg BID x 21 d, then 20 mg daily (w/ same time each day) 5 mg BID 10 mg BID x 7 d, then 5 mg BID 60 mg daily 60 mg daily (p 5-10 d. of parenteral AC) 150 mg BID 10 mg daily (w/ or w/out food), after > 6 mo. Initial tx 2.5 mg BID, after > 6 mo. Initial tx N/A N/A N/A N/A

13 Dabigatran (PRADAXA) 1 Rivaroxaban (XARELTO) 2 Apixaban (ELIQUIS) 3 Edoxaban (SAVAYSA) 4 Betrixaban (BEVYXXA) 5 FDA Approved Indications/STANDARD Dosing Prophylaxis of DVT following hip replacement surgery 110 mg x 1 day, then 220 mg daily 10 mg daily x 35 d (w/ or w/out food, start 6-10 h p hemostasis) 2.5 mg BID x 35 d (start h postop) Prophylaxis of DVT following knee replacement surgery Prophylaxis of VTE in adults hospitalized for acute illness at risk d/t mobility, etc. Reduction of risk of major CV events in patients with chronic CAD or PAD N/A N/A N/A 10 mg daily x12d (w/ or w/out food, start 6-10 h p hemostasis) 2.5 mg BID x12d (start h postop) N/A N/A 2.5 mg BID (w/ or w/out food) w/ ASA mg daily N/A N/A N/A N/A N/A N/A N/A 160 mg x 1 st dose, then 80 mg daily w/ food (x d) N/A

14 Antithrombotic Tx for AF CHEST (2018) Tx with DOAC or VKA recommended for CHA 2 DS 2 - VASc >1 male, >2 female [strong rec, mod. qual. evid] Chest. 137(2): Chest. 154(5):

15 Antithrombotic Tx for AF CHEST DOAC (NOAC) preferred over VKA as oral anticoagulant a Consider cost/coverage, preferences, adherence to INRs Consider strategies to improve time in therapeutic range (TTR) or conversion to DOAC if < 65% on VKA a a Strong rec, mod. qual. evid Chest. 154(5): JAMA. 2015;313(19):

16 Antithrombotic Tx for AF - CHEST Choice of DOAC High risk of ischemic stroke: dabigatran 150 mg BID [remark] High (GI) bleed risk: apixaban, dabigatran 110 mg BID, or edoxaban [weak rec, very low qual. evid.] ESRD on hemodialysis: VKA preferred to DOAC, but apixaban 5 mg BID is approved for use [ungraded consensus statement & remark] DOAC not recommended if pregnant (or attempting) or breastfeeding [ungraded consensus statement] Chest. 154(5):

17 Antithrombotic Tx for VTE CHEST (2016) DVT of leg or PE, (-) cancer: dabigatran, rivaroxaban, apixaban, or edoxaban preferred vs. VKA for longterm (3 mo.) anticoagulation [Grade 2B] Cancer-associated thrombosis: low-molecular weight heparin (LMWH) preferred as long-term anticoagulation vs. VKA [Grade 2B] or above DOACs [Grade 2C] Recurrent VTE while on DOAC: at least 1 mo. Trial switch to LMWH [Grade 2C] Chest. 149(2):

18 Antithrombotic Tx & Prevention of Thrombosis CHEST (2012) Acutely ill hospitalized medical increased risk of thrombosis anticoagulation w/ LMWH, lowdose unfractionated heparin (LDUH) BID or TID, or fondaparinux [Grade 1B] Low risk thrombosis no prophylaxis recommended [1B] Bleeding or high risk for bleed mechanical prophylaxis [2C], no pharmacologic prophylaxis [1B] Chest. 141(2):7S47S.

19 Antithrombotic Tx & Prevention of Chest. 141(2):7S47S. Thrombosis CHEST (2012) THA or TKA: antithrombotic x days (LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH, VKA, ASA [1B] or intermittent pneumatic compression device (IPCD) [1C] Suggest LMWH as preferred tx [2C vs. VKA or ASA, 2B vs. others], partly d/t lack of long-term safety data Pts declining injections or IPCD: recommend apixaban or dabigatran (or rivaroxaban or VKA if unavailable) [1B] Suggest extending to 35d [2B] Pharmacologic + IPCD in hospital [2C] Inc. bleeding risk: IPCD or no prophylaxis vs. pharm [2C]

20 Checkpoint #1 Which of the following agents does not affect the activity of Factor Xa? a) Warfarin b) Dabigatran c) Rivaroxaban d) Apixaban e) Edoxaban

21 Checkpoint #1 Which of the following agents does not affect the activity of Factor Xa? a) Warfarin b) Dabigatran c) Rivaroxaban d) Apixaban e) Edoxaban

22 Checkpoint #2 Which of the following agents is not FDA approved for the treatment of non-valvular AF? a) Dabigatran b) Rivaroxaban c) Apixaban d) Edoxaban e) Betrixaban

23 Checkpoint #2 Which of the following agents is not FDA approved for the treatment of non-valvular AF? a) Dabigatran b) Rivaroxaban c) Apixaban d) Edoxaban e) Betrixaban

24 Objectives At the completion of this activity, the participant will be able to Discuss the role of direct oral anticoagulants (DOACs) in anticoagulation, including agents FDA-approved indications and place within guidelines. Recommend appropriate dosing (or possibly avoidance) of specific DOACs based on indication and patient-specific factors, including drug interactions. Formulate a monitoring plan for patients on DOACs.

25 Contraindications Active Pathological Bleeding Severe Hypersensitivity Mechanical Prosthetic Heart Valve Dabigatran (PRADAXA) 1 X X X Rivaroxaba n (XARELTO) 2 X X Apixaban (ELIQUIS) 3 X X Edoxaban (SAVAYSA) 4 X Betrixaban (BEVYXXA) 5 X X

26 Black Box Warnings Premature D/C Increases Risk of Thrombotic Events Spinal/Epidural Hematoma Dabigatran (PRADAXA) 1!! Rivaroxaba n (XARELTO) 2!! Apixaban (ELIQUIS) 3!! Edoxaban (SAVAYSA) 4! (ischemic events) Betrixaban (BEVYXXA) 5! Reduced Efficacy in nonvalvular AF Pts w/ CrCl > 95 ml/min!!

27 Dabigatran Pertinent Pharmacokinetics 1 Absorption: High fat meal delays C max 2 hr, but may take w/ or w/o food Bioavailability increases 75% if taken w/out capsule caution against opening/chewing! P-glycoprotein (P-gp) substrate Metabolism Dabigatran etexilate ester hydrolyzed to dabigatran Does NOT interact w/ CYP450 Undergoes glucuronidation to active metabolites Excretion Primarily eliminated in urine T 1/2 = hr in healthy subjects

28 P-glycoprotein DAAs pdf Clin Pharmacol & Ther. 93(1):68-77.

29 Dabigatran Dose Adjustments 1 Indication Circumstance Dosage Reduction in risk of stroke & systemic embolism in nonvalvular AF CrCl > 30 ml/min CrCl ml/min CrCl < 15 ml/min or on dialysis P-gp Inhibitor (dronedarone or systemic ketoconazole) + CrCl ml/min P-gp inhibitor + CrCl < 30 ml/min 150 mg BID 75 mg BID No recommendations 75 mg BID Avoid

30 Dabigatran Dose Adjustments 1 Indications Circumstance Dosage Tx of DVT/PE CrCl > 30 ml/min 150 mg BID Reduction in risk of recurrence of DVT/PE Prophylaxis of DVT/PE following hip replacement CrCl < 30 ml/min or dialysis P-gp inhibitor + CrCl < 50 ml/min CrCl > 30 ml/min CrCl < 30 ml/min or dialysis P-gp inhibitor + CrCl < 50 ml/min No recommendations Avoid 110 mg x day 1, then 220 mg daily No recommendations Avoid Swallow whole w/ full glass water, w/ or w/out food Missed dose: Take ASAP; skip if < 6 h to next dose

31 Dabigatran A Matter of Time 1 1 st dose when converting from: Warfarin: when INR < 2.0 Parenteral AC: 0-2 hr before next dose due (or at time of D/C if UFH infusion) See PI for recommendations in other direction Surgery: D/C 1-2 d prior if CrCl > 50 ml/min D/C 3-5 d prior if CrCl < 50 ml/min Longer times for major surgery, spinal puncture, placement of spinal/epidural catheter/port Restart when medically appropriate

32 Dabigatran Other Warnings/Precautions 1 Bleeding Investigate decrease in Hgb/Hct, hypotension Reversal agent: Idarucizumab (PRAXBIND) Emergent surgery/procedures, life-threatening/uncontrolled bleed Dialyzable, but limited clinical experience Consider platelet concentrates if thrombocytopenic or long-acting antiplatelet co-therapy Caution w/ use of other drugs which increase risk (e.g. ASA/NSAIDs, P2Y12 inhibitors, SSRI/SNRI, other anticoag/thrombolytics) CI w/ mechanical heart valve, not recommended w/ other prosthetic valves d/t lack of evidence Avoid use w/ P-gp inducers

33 Dabigatran Special Populations 1 Pregnancy Limited data Lactation Not recommended Pediatrics Safety/efficacy not established Geriatrics Risk-benefit favorable in all age groups

34 Rivaroxaban Pertinent Pharmacokinetics 2 Absorption: 2.5 mg, 10 mg tabs bioavailability unaffected by food 15 mg, 20 mg tabs bioavailability increased by food Avoid administration distal to stomach lower absorption Metabolism CYP 3A4/5, 2J2, hydrolysis to inactive metabolites (51% of dose) Excretion 36% unchanged in urine, 7% in feces P-gp, ATP-binding cassette G2 (ABCG2) transporter substrate t 1/2 = 5-9 hr in healthy subjects

35 Rivaroxaban Drug Interactions 2 Avoid use w/ combined P-gp & strong CYP3A inhibitors (e.g. ketoconazole & ritonavir) or inducers (e.g. carbamazepine, phenytoin, rifampin, St. John s Wort) Exception: change in exposure w/ clarithromycin unlikely to affect bleeding risk Shouldn t be used w/ combined P-gp & moderate CYP3A inhibitors (e.g. erythromycin) in renal impairment (CrCl 15 - <80 ml/min) unless benefit > risk See Warnings/Precautions

36 Rivaroxaban Dose Adjustments 2 Indications Circumstance Dosage Reduction in risk of stroke in nonvalvular AF CrCl < 50 ml/min 15 mg daily Tx, reduction in risk of recurrence, or prophylaxis of DVT/PE Reduction of risk of major cardiovascular events in chronic CAD/PAD CrCl < 30 ml/min No dose adjustment needed for CrCL Avoid N/A Administration: see dosing chart; stable crushed in water/applesauce x 4 hr Missed dose: 2.5 mg BID: skip 15 mg BID: take immediately (may take at same time as next dose to get 30 mg/day) Daily dosing: Take ASAP, but do not double dose

37 Rivaroxaban A Matter of Time 2 1 st dose when converting from: Warfarin: when INR < 3.0 Other anticoagulants: 0-2 hr before next PM dose due (or at time of D/C of UFH infusion) See PI for recommendations in other direction Surgery: D/C for at least 24 hours prior Restart once hemostasis established

38 Rivaroxaban Other Warnings/Precautions 2 Bleeding Reversal agent available: Andexanet alfa (ANDEXXA) Not dialyzable (protein bound) Consider pharmacodynamic drug interactions Safety/efficacy not established w/ prosthetic heart valves NOT recommended as acute alternative to UFH in PE w/ hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy

39 Rivaroxaban Special Populations 2 Pregnancy Limited data Lactation Present in human milk; limited data on effects Pediatrics Safety/effectiveness not established Geriatrics Risk-benefit favorable in all age groups Hepatic Impairment AUC increase of 127% in moderate (Child-Pugh B) hepatic impairment; avoid use in Child-Pugh B/C or hepatic disease w/ coagulopathy

40 Apixaban Pertinent Pharmacokinetics 3 Absorption: Bioavailability not affected by food Metabolism 25% dose recovery as inactive metabolites CYP3A4; 1A2, 2C8, 2C9, 2C19, 2J2 (minor) Excretion 27% renal t 1/2 = 12 hr P-gp & breast cancer resistance protein substrate

41 Apixaban Drug Interactions 3 Combined P-gp and strong 3A4 inducers (rifampin, carbamazepine, phenytoin, St. John s Wort) avoid use together See Dosing/Warnings/Precautions

42 Apixaban Dose Adjustments 3 Nonvalvular AF: Reduce dose to 2.5 mg BID IF 2+ of these factors present: Age > 80 y.o. Wt < 60 kg SCr > 1.5 mg/dl Administration w/ combined P-gp and strong 3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir): 5 or 10 mg BID: Reduce dose 50% (except clarithromycin) 2.5 mg BID: Avoid use Administration: May crush & suspend in water, D5W, apple juice, or mixed w/ applesauce (stable x 4 hr) Missed dose: Take ASAP, but do not double dose

43 Apixaban A Matter of Time 3 1 st dose when converting from: Warfarin: when INR < 2.0 Other anticoagulants: at time next dose would be due See PI for recommendations in other direction Surgery: D/C at least 48 hr prior if moderate-high risk of unacceptable/clinically significant bleeding 24 hr prior if low risk of bleeding or in non-critical area/easily controlled Restart after hemostasis established

44 Apixaban Other Warnings/Precautions 3 Bleeding Effect persists 24 hr after last dose Reversal agent available: Andexanet alfa (ANDEXXA) Activated oral charcoal reduces absorption No substantial effect from hemodialysis Consider pharmacodynamic drug interactions Safety/efficacy not established w/ prosthetic heart valves NOT recommended as acute alternative to UFH in PE w/ hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy

45 Apixaban Special Populations 3 Pregnancy Category B only if benefit > risk Lactation Excretion unknown not compatible Pediatrics Safety/effectiveness not established Geriatrics Risk-benefit favorable in all age groups Hepatic Impairment Moderate/ Child-Pugh B: no dosing recommendations can be provided; consider possible coagulopathies Severe/ Child-Pugh C: not recommended

46 Edoxaban Pertinent Pharmacokinetics 4 Absorption: Food does not affect exposure Distribution Biphasic: SS reached w/in 3 days Metabolism Minimal hydrolysis (M-4 predominant active metabolite 10% of exposure of active molecule), conjugation, and CYP 3A4 oxidation Excretion Primarily as unchanged drug in urine (50% total clearance) SHOULD NOT BE USED IN AF if CrCl > 95 ml/min t 1/2 = hr

47 Edoxaban Drug Interactions 4 P-gp inducers: avoid w/ rifampin P-gp inhibitors: PE/DVT: Adjust dose AF: Do NOT adjust dose ENGAGE AF-TIMI 48: Dose reduction for P-gp inhibitor resulted in lower levels than in patients receiving full dose

48 Edoxaban Dose Adjustments 4 Indications Circumstance Dosage CrCl > 95 ml/min DO NOT USE Nonvalvular AF CrCl ml/min 30 mg daily Tx of DVT/PE CrCl < 15 ml/min CrCl ml/min OR Wt < 60 kg OR P-gp inhibitors NOT REC 30 mg daily CrCl < 15 ml/min NOT REC Administration: With/without food; may give crushed in 2-3 oz water or applesauce Missed dose: Take ASAP on same day, do not double

49 Edoxaban A Matter of Time 4 1 st dose when converting from: VKA: when INR < 2.5 Other oral anticoagulants, LMWH: when next dose due UFH: 4 hours after infusion D/C See PI for recommendations in other direction Surgery: D/C at least 24 hour prior Restart once hemostasis achieved (1-2 hr to effect)

50 Edoxaban Other Warnings/Precautions 4 Bleeding No established way to reverse (anticoagulant effect lasts 24 hr after last dose) May consider PCC, APCC, or rfviia not evaluated in clinical outcome studies In PD studies (healthy subjects, single dose), ETP returned to preedoxaban baseline in 0.5 hr after initiating 15 min infusion of 50 IU/kg PCC, continued to increase to ~40% above 22 hr Hemodialysis does not substantially clear Consider pharmacodynamic interactions Safety/efficacy not established w/ mechanical heart valves, moderate-severe mitral stenosis

51 Edoxaban Special Populations 4 Pregnancy Data insufficient to evaluate risk Lactation Not recommended Pediatrics Safety/effectiveness not established Geriatrics Similar safety/efficacy as in younger patients Hepatic Impairment Child-Pugh A: no adjustment required Child-Pugh B/C: not recommended (possible intrinsic coagulation disorders)

52 Betrixaban Pertinent Pharmacokinetics 5 Absorption: P-gp substrate C max & AUC reduced by food intake w/in previous 6 hrs Metabolism CYP-independent hydrolysis 2 major inactive metabolites (15 18% circulating) < 1% CYP-related Excretion 85% in feces, 11% in urine t 1/2 = hr

53 Betrixaban Dose Adjustments 5 Indication Circumstance Dosage Prophylaxis of VTE in adults hospitalized for acute medical illness at risk d/t moderate/severe restricted mobility and other risk factors CrCl 15 - <30 ml/min (Cockcroft-Gault, ACTUAL body weight) OR P-gp inhibitors Both of above 80 mg x 1 dose, then 40 mg daily AVOID USE Duration: days Administration: at same time of day with food (capsule) Missed dose: take ASAP same day; do not double

54 Betrixaban A Matter of Time 5 No guidance provided in PI on conversion from/to other agents Surgery: D/C at least 72 hr before removal of epidural catheter; do not resume administration until 5 hour after removal

55 Betrixaban Other Warnings/Precautions 5 Bleeding No established way to reverse (72 hr duration of effect after last dose) Effect of hemodialysis unknown Consider PD interactions Safety/efficacy not established in Pts w/ prosthetic heart valves

56 Betrixaban Special Populations 5 Pregnancy No data on use in pregnant women; only use if benefit>risk Lactation No data available Pediatrics Safety/effectiveness not established Geriatrics No safety/effectiveness differences between older/younger Pts Hepatic Impairment Not evaluated (d/t potential intrinsic coagulopathies)

57 Checkpoint #3 Interactions involving CYP3A4 are most relevant to: a) Dabigatran b) Rivaroxaban c) Apixaban d) Edoxaban e) Betrixaban f) b & c

58 Checkpoint #3 Interactions involving CYP3A4 are most relevant to: a) Dabigatran b) Rivaroxaban c) Apixaban d) Edoxaban e) Betrixaban f) b & c

59 Checkpoint #4 Which of the following DOACs are stable crushed in water (e.g. if administration via NG tube required)? [CHOOSE ALL THAT APPLY] I. Dabigatran II. III. Rivaroxaban Apixaban IV. Edoxaban V. Betrixaban

60 Checkpoint #4 Which of the following DOACs are stable crushed in water (e.g. if administration via NG tube required)? [CHOOSE ALL THAT APPLY] I. Dabigatran II. III. Rivaroxaban Apixaban IV. Edoxaban V. Betrixaban

61 Objectives At the completion of this activity, the participant will be able to Discuss the role of direct oral anticoagulants (DOACs) in anticoagulation, including agents FDA-approved indications and place within guidelines. Recommend appropriate dosing (or possibly avoidance) of specific DOACs based on indication and patient-specific factors, including drug interactions. Formulate a monitoring plan for patients on DOACs.

62 Monitoring CHEST AF Guidelines: Bleeding risk each encounter, focused on modifiable risk factors a More frequent f/u if high bleeding risk (HAS-BLED >3) b a Strong rec, low qual. evid.; b Strong rec, mod. qual. evid. Chest. 154(5):

63 Monitoring Labs generally not required/recommended to assess level of anticoagulation 1-5 INR not an accurate assessment of safety/effectiveness Dabigatran: aptt or ECT if monitoring needed 1

64 Checkpoint #5 Which of the following is LEAST appropriate as part of a patient s routine follow-up when taking a DOAC? a) BMP and calculation of CrCl b) Weight measurement c) INR d) HAS-BLED calculation e) Assessment of adherence f) Education on stroke and/or VTE sx

65 Checkpoint #5 Which of the following is LEAST appropriate as part of a patient s routine follow-up when taking a DOAC? a) BMP and calculation of CrCl b) Weight measurement c) INR d) HAS-BLED calculation e) Assessment of adherence f) Education on stroke and/or VTE sx

66 Patient Case LZ is a 73 y.o. WF s/p R THA. Allergies: NKDA PMH: hyperlipidemia, T2DM, seizure disorder SH: (-) for smoking, EtOH, & substance abuse Home Meds: Ferrous sulfate 50 mg BID Phenytoin ER 100 mg - 3 BID Potassium Cl ER 10 meq daily Phenobarbital 60 mg BID Diltiazem 120 mg tab BID Metformin 1000 mg BID CC Atorvastatin 80 mg daily Furosemide 40 mg qam Pantoprazole 40 mg daily VS/Labs: Wt: 104 kg SCr: 0.5 mg/dl

67 Discharge Medications: Patient Case Apixaban 2.5 mg PO BID x 30 d Oxycodone/APAP 5/325 mg 1-2 tab PO q4h PRN pain/spasm (Continue home medications) What is your assessment/recommendation? Anticoagulation/DOAC indicated? Agent appropriate? Dose appropriate? Duration appropriate? How should Pt be monitored? What/how would you communicate to MD/Pt?

68 Package Insert Links (via Dailymed) 1. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim; Accessed 2018 Jan Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals; Accessed 2018 Jan Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb; Accessed 2018 Jan Savaysa [package insert]. Basking Ridge, NJ: Daiichi Sankyo; Accessed 2018 Jan Bevyxxa [package insert]. S San Francisco, CA: Portola Pharmaceuticals; Accessed 2018 Jan 2.

69 The (Hopefully) Bloodless Battle for Safe Use of DOACs Gale E. Garmong, PharmD Clinical/Staff Pharmacist Klingensmith s Drug Stores g.garmong@gmail.com