The Script A Publication of the Department of Pharmacy, Norman Regional Health System The Script Congratulate the NRHS Pharmacy Residents By Kim Whitley, Pharm.D., BCPS In This Issue:

Norman Regional Health System offers a yearlong accredited Post Graduate Year 1 (PGY1) Pharmacy Residency that begins each year in July and ends in June the following year. It allows pharmacists to accelerate their growth beyond entry-level competencies, to refine their clinical Congratulate the NRHS skills in a broad range of disease states and to provide evidence-based, patient-centered medication Pharmacy Residents ...... 1 therapy. Residents are also cross-trained in distribution activities and can be found staffing at the Drip HealthPlex on Monday through Thursday evenings. Our pharmacy residents for the 2015-2016 year Monitoring ...... 2, 5 were: Christopher Brown, Jacqueline Medina and Whitney Rohlman. Christopher Brown was Comparison of raised in Norman, OK. He Oral ...... 3-4 graduated from the University of Oklahoma Critical Medication Shortages . . . . . 5 College of Pharmacy in Pharmacy and Therapeutics 2015 with special Committee Update...... 6 distinction and a leadership track degree Direct Oral Anticoagulants option. His current (DOAC): Focus on pharmacy interests include (Savaysa®) ...... 6 internal medicine, infectious diseases, and leadership. Chris will remain on staff after completing the NRHS PGY1 We welcome your thoughts, residency program. comments and/or suggestions.

Left to right: Whitney Rohlman, Jacqueline Medina, and Chris Brown Jacqueline Medina was Do you have an idea for a story? Is there born and raised in Deming, information we can provide you? New Mexico. She is a 2015 graduate from the University of New Mexico College of Pharmacy in Albuquerque, NM and moved to Norman, OK to complete her clinical pharmacy residency. All correspondence concerning Jacqueline’s current interest areas include ambulatory care, psychiatry and transitions of care. After The Script should be sent to: completion of her residency, Jacqueline will be employed as a staff pharmacist at The Hospitals of Providence in El Paso, TX. Lisa Mayer, Pharm.D., BCPS 901 N Porter Ave., Box 1308 Whitney Rohlman was born in Oklahoma City, OK. She is a 2015 graduate of the University of Oklahoma College of Pharmacy. Her current pharmacy interests include cardiology, internal Norman, OK 73070 medicine and infectious diseases. After completion of her residency, Whitney plans to obtain a [email protected] Board Certified Pharmacotherapy Specialist (BCPS) certification. She will also remain on staff at NRHS. Each resident undertakes a project during their residency, in which they present the research at local and national pharmacy conferences throughout the year. Chris’s project was a medication use evaluation and cost minimization analysis of injectable nicardipine. Jacqueline’s project involved the development and implementation of a heparin-induced thrombocytopenia protocol and its impact on patient care and cost. Whitney’s project focused on the appropriateness of medications removed on override from the Pyxis machines and the benefits of implementing an ongoing quality assurance program. Please congratulate our current pharmacy residents as they finish the last month of their residency this June!

The Script Spring 2016, Issue 7

Heparin Drip Monitoring By Lysse Vadder, Pharm.D. Unfractionated heparin (UFH) has multiple indications for treatment and prevention of thrombotic events. Higher doses of heparin are used for the treatment of acute venous thrombosis while lower doses are used for prevention of venous thrombosis. Typically, heparin is administered via IV infusion for treatment due to its short half-life, which also makes it easy to titrate to effect. The Institute for Safe Medication Practices considers IV UFH a high-alert medication since it bears a heightened risk of causing significant patient harm when it’s used incorrectly, so it’s important to be well informed on its use. Norman Regional Health System (NRHS) uses weight-based dosing protocols when dosing heparin for treatment of acute venous thrombosis. Currently, there are two order sets that contain the heparin drip protocols. The Deep Vein Thrombosis AND/OR Pulmonary Embolism (DVT/PE), which is the most common order set used at NRHS, and the Cardiac Patients, Anticoagulation order set which is typically used for patients with an acute (AMI), atrial fibrillation, or heart valve replacement. Prior to the initiation of these order sets, a dry weight must be recorded in kilograms upon initiation of the order set. This initial weight is used to calculate the initial bolus dose as well as ALL rate changes for the heparin drip. Once this initial weight is recorded in the IV pump, it should NOT be updated. Heparin is currently monitored using the anti-Xa level, which measures both the intrinsic and extrinsic pathways of the coagulation cascade. Historically, heparin was monitored using the activated partial thromboplastin time (aPTT), but this was found to less reliable since it measures the intrinsic pathway only. When a patient is started on a heparin drip protocol, it is imperative to pick the correct order set for the patient/indication since the initial bolus and rate, rate changes, and re-bolus differ between the two order sets. Once the correct order set is chosen, a baseline heparin anti- Xa level must be drawn before the heparin bolus/drip is initiated. The anti-Xa level should be repeated 6 hours after initiation of the heparin drip and with each rate change per protocol. Once the anti-Xa level is within therapeutic range (0.3 to 0.7 units/mL), the monitoring frequency is reduced to every morning.

Cardiac Patients, Anticoagulation Order Set

§ Bolus - heparin sodium 60 unit/kg IV ONCE, MAXIMUM of 4,000 units (round to nearest 100 units) § Continuous Infusion - heparin sodium 25,000 units/500 mL IV at initial rate of 12 units/kg/hr, MAXIMUM initial rate of 1,000 units/hr

Heparin Xa STOP Bolus Rate Change Recheck (units/mL) Infusion Hold until Heparin Xa level less than 1.2, if two consecutive GREATER THAN 1.2 NO YES STAT in 1 hr results greater than 1.2 notify, physician 1.01 to 1.2 NO YES Hold for 1 HOUR, then resume and reduce rate by 3 units/kg/hr 6 hrs 0.71 to 1.0 NO NO Reduce rate by 2 units/kg/hr 6 hrs GOAL 0.3 to 0.7 NO NO NO CHANGE In AM 0.15 to 0.29 NO NO Increase rate by 1 units/kg/hr 6 hrs LESS THAN 0.15 NO NO Increase rate by 2 units/kg/hr 6 hrs

Anticoagulation, Deep Vein Thrombosis AND/OR Pulmonary Embolus Order Set

§ Bolus - heparin sodium 80 unit/kg IV ONCE (round to nearest 100 units) § Continuous Infusion - heparin sodium 25,000 units/500 mL IV at initial rate of 18 units/kg/hr § Note: there is NO MAXIMUM bolus dose or MAXIMUM initial rate for this order set

Heparin Xa STOP Bolus Rate Change Recheck (units/mL) Infusion Hold until Heparin Xa level less than 1.2, if two consecutive GREATER THAN 1.2 NO YES STAT in 1 hr results greater than 1.2 notify, physician 1.01 to 1.2 NO YES Hold for 1 HOUR, then resume and reduce rate by 3 units/kg/hr 6 hrs 0.71 to 1.0 NO NO Reduce rate by 1 units/kg/hr 6 hrs GOAL 0.3 to 0.7 NO NO NO CHANGE In AM 0.15 to 0.29 40 units/kg NO Increase rate by 2 units/kg/hr 6 hrs LESS THAN 0.15 80 units/kg NO Increase rate by 4 units/kg/hr 6 hrs

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2 The Script Comparison of Oral Anticoagulants Spring 2016, Issue 7 Coumadin® () Eliquis® () Savaysa® (edoxaban) Xarelto® () Pradaxa® () Category/ Vitamin K Antagonist: Factor Xa Inhibitor: Factor Xa Inhibitor: Factor Xa Inhibitor: Direct Inhibitor: Mechanism of Inhibits formation of vitamin K Directly inhibits factor Xa Directly inhibits factor Xa Directly inhibits factor Xa Directly inhibits thrombin dependent clotting factors (II, VII, IX, Action X) and proteins C & S Indications and Venous Thromboembolism (VTE) Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Usual Doses Treatment 5 mg PO BID 60 mg PO daily 20 mg PO daily with food 150 mg PO BID 2.5 mg PO BID, if at least 2 factors: VTE Prophylaxis in Patients with (not - Age ≥ 80 yrs DVT/PE Treatment DVT/PE Treatment DVT/PE Treatment an all inclusive list): - Weight ≤ 60 kg § 60 mg PO daily (AFTER 5-10 days of 15 mg PO BIDWM x 21 days, then 20 150 mg PO BID (AFTER 5-10 days of a § Atrial fibrillation/flutter - SCr ≥ 1.5 mg/dL a parenteral ) mg PO daily with food parenteral anticoagulant) § Heart valve replacement § Weight ≤ 60 kg: 30 mg PO daily § Hypercoagulable disorder DVT/PE Treatment § Concomitant therapy with specific DVT/PE Secondary Prophylaxis § Idiopathic pulmonary artery 10 mg PO BID x 7 days, then 5 mg PO P-gp inhibitors (ie, verapamil, 20 mg PO daily with food hypertension BID quinidine; the short-term use of Post-op VTE Prophylaxis for Hip § Left ventricular azithromycin, clarithromycin, Replacement § Total hip or knee replacement DVT/PE Secondary Prophylaxis erythromycin, oral itraconazole, 2.5 mg PO BID AFTER 6 months of 10 mg PO daily x 35 days surgery oral ketoconazole): 30 mg PO once VTE treatment daily Post-op VTE Prophylaxis for Knee - Variable dose based on INR Replacement - Starting dose: 2-10 mg PO daily Post-op VTE Prophylaxis for Hip 10 mg PO daily x 12-14 days (lower starting doses may be Replacement required for patients with hepatic 2.5 mg PO BID x 35 days impairment, poor nutrition, CHF, Post-op VTE Prophylaxis for Knee elderly, high risk of bleeding or Replacement who are debilitated) 2.5 mg PO BID x 12 days Renal Dose § None Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Nonvalvular Atrial Fibrillation Adjustments § Warfarin remains drug of choice § ESRD on HD: 5 mg PO BID § CrCl > 95 mL/min: avoid use § CrCl = 15-50 mL/min: 15 mg PO § CrCl = 15-30 mL/min: 75 mg PO BID for patients with severe or end- § ESRD on HD (≥ 80 yoa OR weight ≤ § CrCl 51-95 mL/min: 60 mg PO daily daily with food § ESRD on HD or CrCl <15 mL/min: stage chronic kidney disease per 60 kg): 2.5 mg PO BID § CrCl 15-50 mL/min: 30 mg PO daily § CrCl < 15 mL/min or ESRD: avoid avoid use (AHA/ACC/HRS 2014 AHA/ACC/HRS 2014 § Patients with SCr > 2.5 mg/dL or § CrCl < 15 mL/min: avoid use use (AHA/ACC/HRS 2014 don't don't recommend) CrCl < 25 mL/min were excluded recommend) § Patients with CrCl < 30 mL/min from the ARISTOTLE and AVERROES DVT/PE Treatment § Patients with CrCl <30 mL/min were were excluded from the RE-LY trial trials § CrCl 15-50 mL/min: 30 mg PO daily excluded from the ROCKET-AF trials § Contraindicated with CrCl ≤ 30 § CrCl < 15 mL/min: avoid use mL/min per ACCP DVT/PE Treatment/Prophylaxis DVT/PE Treatment/Prophylaxis § No dosage adjustment *Use ACTUAL BODY WEIGHT for CrCl* § CrCl < 30 mL/min: avoid use DVT/PE Treatment § Patients with SCr > 2.5 mg/dL or § Patients with CrCl <30 mL/min were § HD or CrCl ≤ 30 mL/min: no dosage CrCl < 25 mL/min were excluded excluded from the EINSTEIN-DVT recommendations from the AMPLIFY and AMPLIF-EXT and EINSTEIN-PE trials § Patients with CrCl < 30 mL/min or trials on HD were excluded from the RE- Post-op VTE Prophylaxis for Hip/Knee COVER and RE-COVER II trials. Post-op VTE Prophylaxis for Hip/Knee Replacement Replacement § CrCl < 30 mL/min or ESRD: avoid *Use ACTUAL BODY WEIGHT for CrCl* § No dosage adjustment use § Patients with CrCl < 30 mL/min § Patients with CrCl < 30 mL/min were excluded from the ADVANCE- were excluded from the RECORD 1, 1, -2, and -3 trials. 2 & 3 trials.

*Use ACTUAL BODY WEIGHT for CrCl* *Use ACTUAL BODY WEIGHT for CrCl* Pharmacokinetic Onset: 24-72 hrs Time to peak: 3-4 hrs Time to peak: 1-2 hrs Time to peak: 2-4 hrs Time to peak: 1 hr (2 hrs with food) Parameters Peak therapeutic effect: 5-7 days Half-life: ~12 hrs Half-life: 10-14 hrs Half-life: 5-9 hrs (11-13 hrs in elderly) Half-life: 12-17 hrs Half-life: 20-60 hrs (mean of 40 hrs) Metabolism Cytochrome P450 (CYP) 2C9, 3A4, § CYP 3A4, 3A5 § CYP 3A4 (minor) § CYP 3A4, 3A5, 2J2 § Hepatic glucuronidation 2C19, 1A2 § P-glycoprotein substrate § P-glycoprotein substrate § P-glycoprotein substrate § P-glycoprotein substrate 3 The Script Comparison of Oral Anticoagulants Spring 2016, Issue 7 Coumadin® (warfarin) Eliquis® (apixaban) Savaysa® (edoxaban) Xarelto® (rivaroxaban) Pradaxa® (dabigatran) Interactions § Many drug-drug interactions due § CYP 3A4 inhibitors/inducers – § P-glycoprotein inhibitors/inducers § CYP 3A4 inhibitors/inducers - § Dronedarone or ketoconazole to hepatic metabolism avoid use with strong inducers § Avoid in moderate to severe avoid use with strong inducers with CrCl = 30 to 50 mL/min for § Food-drug Interactions with § P-glycoprotein inhibitors/inducers hepatic impairment § P-glycoprotein inhibitors/inducers - nonvalvular atrial fibrillation: vitamin K – maintain consistent § Avoid grapefruit juice § NSAIDs/antiplatelets avoid use with dual inhibitors of reduce dabigatran to 75 mg PO BID vitamin K intake § Avoid in severe hepatic impairment CYP 3A4 (strong) and P- § P-glycoprotein inducers – avoid use § Avoid cranberry juice § NSAIDs/antiplatelets glycoprotein § P-glycoprotein inhibitors § NSAIDs/antiplatelets § Avoid grapefruit juice § NSAIDs/antiplatelets § Chronic daily ETOH use increases § Avoid in moderate to severe metabolism of warfarin and hepatic impairment decreases the PT/INR § NSAIDs/antiplatelets Monitoring International Normalized Ratio (INR): § None for efficacy § None for efficacy § None for efficacy § None for efficacy Parameters § 2.0-3.0 (Afib, VTE, mechanical AVR) § Renal and hepatic function § Renal and hepatic function § Renal and hepatic function § Renal function § 2.5-3.5 (mechanical AVR w/risk factors and/or mechanical MVR) Side Effects “Purple Toe” syndrome, bleeding, Bleeding, bruising Bleeding Bleeding GI symptoms, bleeding bruising, skin necrosis/gangrene Reversal Strategies § Vitamin K 2.5 to 5 mg PO/IV § No specific § No specific antidote § No specific antidote § (Praxbind®) PO: onset: 6-10 hrs; peak: 24-48 § Activated prothrombin complex § PCC § PCC has been shown to reverse the 5 g IV (administered as 2 separate hrs concentrate (aPCC) § Hemodialysis doesn’t have a anticoagulant effect of rivaroxaban 2.5 g doses NMT 15 min apart) IV: onset: 1-2 hrs; peak: 12-14 hrs § PCC significant impact on edoxaban (Eerenberg, 2011) § PCC is ineffective (Eerenberg, 2011) § Vitamin K IV 1-10 mg + § Activated charcoal 50 g PO if used clearance § Activated charcoal 50 g PO if used § aPCC may be considered prothrombin complex concentrate within 6 hrs of ingestion § There is currently no data for use within 2 hrs of ingestion § Hemodialysis removes ~57% of the (PCC) or fresh frozen plasma (FFP) § Andexanet alfa (pending FDA of activated charcoal § Not dialyzable drug over 4 hrs for major bleeds approval; target FDA action date is § Andexanet alfa (pending FDA § Andexanet alfa (pending FDA § Activated charcoal 50 g PO if used August 17, 2016) approval; target FDA action date is approval; target FDA action date is within 2 hrs of ingestion § PER977 (aripazine) in phase II trials August 17, 2016) August 17, 2016) § PER977 (aripazine) in phase II trials § PER977 (aripazine) in phase II trials § PER977 (aripazine) in phase II trials Pre-op/Pre- § Hold 3-5 days before surgery § Hold at least 48 hrs before surgery § Hold at least 24 hrs before surgery § Hold at least 24 hrs before surgery § CrCl ≥ 50 mL/min: hold 1-2 days procedure § INR should be < 1.5 or invasive procedures with (per manufacturer) before surgery moderate-to-high risk of bleeding § CrCl ≥ 50 mL/min: hold 3 days § CrCl < 50 mL/min: hold 3-5 days Management § Hold at least 24 hrs before surgery before surgery (Wysokinski, 2012) before surgery or invasive procedures with low § CrCl < 50 mL/min: hold 5 days risk bleeding before surgery (Wysokinski, 2012) Other § BBW: May cause major or fatal § BBW† § BBW†: Do not administer to § BBW† § BBW† bleeding § Pregnancy Category B nonvalvular afib patients with CrCl § Pregnancy Category C § Pregnancy Category C § Pregnancy Category X > 95 mL/min (Cockcroft-Gault). In § Administer doses ≥ 15 mg/day with § MUST be swallowed whole (D with mechanical heart valve) clinical trials, these patients had an food (opening, crushing or chewing increased rate of ischemic § May contain lactose, so use is not results in up to 75% increase in with edoxaban 60 mg once daily recommended in patients with absorption and potentially serious compared to patients treated with lactose or galactose intolerance adverse effects) warfarin; use another § Store in original container and anticoagulant in these patients. discard 4 months after opening § Pregnancy Category C § Give with food if dyspepsia occurs § No data are available regarding the § Not recommended in patients with bioavailability upon crushing of valvular heart disease including edoxaban tablets or administration bioprosthetic heart valves through feeding tubes § Use is contraindicated with § Not recommended in patients with mechanical heart valves mechanical heart valves or moderate to severe mitral stenosis †Black Box Warnings (BBW): 1. Premature discontinuation of any oral anticoagulant in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. 2. Spinal or epidural hematomas resulting in long-term or permanent paralysis may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal/epidural puncture; the risk is increased by the use of indwelling epidural catheters with concomitant administration of other drugs that affect hemostasis (eg, NSAIDS, platelet inhibitors, other anticoagulants), in patients with a history of traumatic or repeated epidural or spinal punctures, a history of spinal deformity or surgery, or if optimal timing between the administration of anticoagulant and neuraxial procedures is not known. Consider the potential benefit versus risk prior to neuraxial intervention in patients who are anticoagulated or scheduled to be anticoagulated for thromboprophylaxis. 4 The Script Spring 2016, Issue 7

Heparin Drip Monitoring Continued Pump Instructions Important Points A. Initiation of drip § Choose the appropriate order set for the indication. 1. MUST select the appropriate library (ICU, Cardio, etc.) and press ENTER § Obtain patient’s baseline weight (in kg) via bedscale or standing scale. 2. Select A on pump § Obtain baseline heparin anti-Xa level BEFORE administration of 3. Access drug list, scroll to Heparin 25,000 unit/500 mL, and press ENTER bolus or drip. 4. Choose Standard Program § NEVER change the weight in the IV pump once the initial weight 5. Enter patient weight (in kg) is entered. 6. Enter starting rate in units/kg/hr (12 OR 18 depending on order set) § ALWAYS use a library to select the heparin drip in the IV pump. 7. Enter total volume to be infused (500 mLs) in the VTBI field This is for patients’ safety since this is a high alert medication! § Use ONLY units/kg/hr for the heparin drip rate on the IV pump 8. Press start § Adjust the rate according to the nomogram/protocol using the B. Rate changes appropriate order set. 1. Select A § This is a continuous infusion, DO NOT STOP the infusion UNLESS 2. Enter the new rate, changing the units/kg/hr on the pumps, NOT mL/hr. directed to per the nomogram/protocol or physician. 3. Do NOT update the weight when calculating the rate change (use the § Notify pharmacy if the heparin drip on the MAR DOES NOT have a initial weight ONLY) protocol. 4. You may have to override the weight in Meditech to match the rate change with the pump

To our new Pharmacy Director Brad Foster, Pharm.D.

To our new Vice President of Quality and Performance Improvement Darin Smith, Pharm.D., BCPS, FASHP

To the pharmacists who are now Board Certified Pharmacotherapy Specialists! The pharmacy now has a total of 10 pharmacists with BCPS certification.

Justin Booth Kim Whitley

To the pharmacists who successfully completed the Society of Infectious Diseases Pharmacists Antimicrobial Stewardship certificate program!

Fran Esfahani Brian Hughes

Critical Medication Shortages By Donna Wilk, CPhT

Medication Action Plan Out of stock with no release date. Alternatives include metoclopramide IV/PO, ondansetron IV/PO, prochlorperazine IV/PO, and Droperidol IV scopolamine patches (IV formulation was discontinued). Available on allocation with a release date of July 2016. This shortage affects all medication-filled syringes used in crash carts due to an issue with the device itself. Dextrose 50% syringes and sodium bicarbonate 8.4% syringes have been removed from Emergency Syringes Pyxis machines and replaced with the vials of each product in an effort to reserve syringes for crash carts. Further communication will be sent out to appropriate staff as we determine any other necessary changes we need to make for Pyxis machines and crash carts. IV Product has released and remains available. We currently have a decent supply on hand at this time. Indigo Carmine IV Unavailable with no release date. Alternatives include: indocyanine green, , and isosulfan blue. Available on allocation with an estimated release date of July 2016. This shortage effects all medication-filled PCAs including PCA Cartridges fentanyl, hydromorphone, meperidine and morphine due to an issue with the device itself. We are monitoring usage and have a decent supply on hand at this time. Piperacillin/ Now available. We are currently working on adding it back to the pertinent order sets. Tazobactam (Zosyn®) IV Prochlorperazine IV Now readily available. Thrombin Topical Now available on a daily allocation. We have a decent supply on hand at this time of the 20,000 units syringe spray kits used in Solution (bovine) surgery. Epistaxis kits are also available on allocation. Total Parenteral In addition to the nationwide shortage on dextrose 70% and sterile water used to compound TPNs, we are also experiencing Nutrition (TPN) intermittent supply issues with electrolytes. At this time, we will continue to use premix formulations of Clinimix 5/15 and Components Clinimix 5/15 + Electrolytes for adult TPNs. Baby TPNs are not affected.

5 The Script Spring 2016, Issue 7

Pharmacy and Therapeutics Committee Update Dosage and Drug Indication Usual Dose P&T Action Strength Ceftolozane/ Intra-abdominal infections (IAI); Ceftolozane 1 g 1.5 g IV every 8 hours (for 4 to 14 days for IAI and 7 Added to formulary – Tazobactam UTI (complicated, including and tazobactam days for UTI) restricted to ID (Zerbaxa®) pyelonephritis) 0.5 g IV Edoxaban DVT and PE treatment; 60 mg PO daily (see edoxaban article below for 15, 30 and 60 mg Added to formulary (Savaysa®) nonvalvular atrial fibrillation dose adjustments) tablets IdaruCIZUMAB 5 g IV (administered as two separate 2.5 g doses, no 2.5 g/50 mL IV Added to formulary Reversal of dabigatran (Praxbind®) more than 15 minutes apart) solution with restrictions UA/NSTEMI; STEMI; stable Loading dose: 25 mcg/kg over 5 min or less. 50 mcg/mL (100 Added to formulary. Tirofiban ischemic heart disease Maintenance infusion: 0.15 mcg/kg/min for up to mL and 250 mL IV Replaced eptifibatide (Aggrastat®) undergoing elective PCI 24 hr depending upon the indication solution) (Integrilin®) (0.075 mcg/kg/min for CrCl ≤ 60 mL/min)

Direct Oral Anticoagulants (DOAC): Focus on Edoxaban (Savaysa®) By Lisa Mayer, Pharm.D., BCPS This is the first in a series of articles reviewing the direct oral anticoagulants (DOAC). Edoxaban (Savaysa®) is a potent, direct Factor Xa inhibitor approved early 2015 as anticoagulant therapy for three FDA indications: DVT and PE treatment and nonvalvular atrial fibrillation (to prevent stroke and systemic embolism). Edoxaban Dosing DVT and PE Treatment § 60 mg PO daily (AFTER 5-10 days of a parenteral anticoagulant) § CrCl 15-50 mL/min: 30 mg PO daily § Weight ≤ 60 kg: 30 mg PO daily § CrCl < 15 mL/min: avoid use § Concomitant therapy with specific P-glycoprotein inhibitors (ie, *Use ACTUAL BODY WEIGHT for CrCl* verapamil, quinidine; the short-term use of azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole): 30 mg PO once daily Nonvalvular Atrial 60 mg PO daily § CrCl > 95 mL/min: avoid use Fibrillation § CrCl 51-95 mL/min: 60 mg PO daily § CrCl 15-50 mL/min: 30 mg PO daily § CrCl < 15 mL/min: avoid use § *Use ACTUAL BODY WEIGHT for CrCl* Converting FROM warfarin Discontinue warfarin and start edoxaban when INR ≤ 2.5 Converting TO warfarin Discontinue edoxaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of edoxaban would have been due.

Benefit Disadvantages • 1 to 2 hour onset of action, • COST! A co-pay card is available to patients that don’t have state or federally funded prescription insurance. eliminating the need for • No reversal agent currently approved (Annexa™ (andexant alfa) is pending PDA approval and PER997 parental overlap (aripazine) is currently in phase II trials) • No routine monitoring of • No lab test to assess dosing or adherence coagulation tests* • Strict adherence required to maintain effect due to the short half-life of 10 to 14 hours • Fixed dose for all patients • Long-term safety not yet established according to renal function • BBW†: Do not administer to nonvalvular atrial fibrillation patients with CrCl > 95 mL/min (Cockcroft-Gault). In • Only food interaction with clinical trials, these patients had an increased rate of ischemic stroke with edoxaban 60 mg once daily grapefruit juice compared to patients treated with warfarin. An alternate anticoagulant is recommended in these patients. • Fewer drug interactions than • Pregnancy Category C warfarin • No data are available regarding the bioavailability upon crushing and/or mixing of edoxaban tablets into food, liquids, or administration through feeding tubes • Not recommended in patients with mechanical heart valves or moderate to severe mitral stenosis. Patients with a bioprosthetic heart valve, valve repair, or valvuloplasty were included in the ENGAGE AF-TIMI 48 trial. The Script The Quarterly Newsletter of the Department of Pharmacy Editor in Chief: Contributors: (A Lisa Mayer, Pharm.D., BCPS Chris Brown, Pharm.D. Samantha Sepulveda, Pharm.D. Lysse Vadder, Pharm.D. Kim Whitley, Pharm.D.,BCPS Donna Wilk, CPhT Clinical Pharmacy Specialist PGY1 Pharmacy Resident Past PGY1 Pharmacy Resident Past PGY1 Pharmacy Resident Clinical/Staff Pharmacist Clinical Pharmacy Technician

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