2018 Midyear Meeting

Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

October 27, 2018

Program Book LOUISIANA SOCIETY OF HEALTH-SYSTEM PHARMACISTS BOARD OF DIRECTORS AND COMMITTEE CHAIRS

Monica Dziuba—President Joseph G. LeBlanc, Jr.—Immediate Past President Kisha O’Neal Gant—President Elect Katherine Aymond—Secretary Tommy Mannino—Treasurer Elizabeth M. Lafitte—Director at Large Jill Comeau—Director at Large Jason Chou—Director at Large Jessica Brady—Director at Large Jackie Champagne—Technician Representative

Amanda Storer—NLSHP President Savannah Posey—NELSHP President Kristin Howell—SCLSHP President Fahamina Ahmed—SELSHP President Shane Domingue—SWLSHP President Joseph Gary LeBlanc—CLSHP President Alexis Horace—Director-elect Heather Maturin—Director-elect

Jessica Brady-University of Louisiana at Monroe Faculty Liaison Iman Borghol-Xavier University Student Faculty Liaison

Committee Chairs Mike Loftin, Scott Dantonio, Stephanie Thompson– Pharmacy Management and Practice Fancy Manton—Subcommittee on Antimicrobial Stewardship William Kirchain & Jeff Evans– Public Policy Jennifer Smith & Jamie Terrell– Programming & Practitioner Education Dana Jamero– Sub-Committee on Publications Lisa Ross—Membership & Marketing Katherine Aymond—New Practitioners Committee Elizabeth Lafitte —Midyear Meeting Coordinator Table of Contents

General Information & Activities……………………………………………………………………..……..1

Midyear Meeting Program………………………………………………………...……………...………..…..3

Sponsors & Exhibitors………………….…………………………………………………………………….…..5

Syllabus (listed chronologically) Pain Mangement and the Opioid Crisis……………………………………………………...…….……..6 Brittany Lines, PharmD

A Whole New Monster: Cancer Survivorship…………………….…………….……………...... …..18 Allison Reed, PharmD

In the Hood: <797/800> Edition ……………………………..………………….….…………..…...…..27 Dylan LeBlanc, PharmD

Hemostatic agents and their uses in coagulation disorders ..……………………..……...…38 Logan Murray, PharmD

Pharmacy Legislative and Administrative Update..…………….….……………...……..……....48 Jeff Evans, PharmD

Current trends and topics in diabetes management ..…………….….……………....………....56 Jamie Terrell, PharmD

Are you ready? Disaster preparedness and response for the pharmacy team.…..…..64 Jennifer Smith, PharmD, BCPS

"Put it in reverse!": Strategies for reversal of anticoagulants ………………………….….…73 , PharmD

Molli Gremillion

General Information & Activities Registration The Midyear Meeting Registration and Information Desk will be open from 7:00 a.m.-4:00 p.m.

Badges Badges must be worn at all times. Badges are required for admittance to all Midyear Meeting functions. Registrants, staff, guests and speakers have white badges. Exhibitors have blue badges.

Meeting Locations All meeting sessions and exhibits will be held on the 2nd level of the Shreveport Convention Center. Please consult the program-at-a-glance or the schedule in this program book for specific meeting room locations.

Continental Breakfast There will be a continental breakfast from 7:00-7:45 a.m. in the Pre-Function Area on the 2nd floor.

Exhibit Program The exhibit program is located in Ballroom C&D on the 2nd level of the Shreveport Convention Center from 11:00 a.m. to 12:00 p.m. Our exhibitors then join us for lunch at noon. Please take time to visit our exhibitors and express your thanks for their participation. Additionally, please thank your local representative whom you see regularly at your practice site.

Lunch Lunch is provided for all paid registrants and exhibitors. Lunch will be served in the Exhibit Area of Ballroom C&D at 12:00 p.m.; lunch will not be served prior to 12:00 pm. Please remember bring the lunch ticket found in your packet with you; lunch is only served to those with a ticket. Spouses/ guests are invited to attend lunch for $25 per ticket, purchased in advance.

Continuing Education Credit The Louisiana Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. A total of 8 contact hours (0.80 CEUs) are scheduled for Saturday’s program, of which a maximum of 6 hours (0.6 CEUs) may be earned by an individual participant.

Evaluations Activity evaluations are extremely important in the development of educational needs assessment for future programs. Please take a moment to evaluate each CE activity you attend; we appreciate and value your input. A booklet of evaluations was included in your registration packet. Please personally turn in your evaluation packet at the end of the meeting, or after attending your last CE activity. We must collect this evaluation packet for you to receive CE credit for the activities at this meeting. Also, a separate general meeting evaluation form is in your packet. Please complete it and turn it in at the registration desk.

1 General Information & Activities, continued

Certification of Continuing Education Hours/ How to Receive Credit: To receive credit for continuing education activities at the Midyear Meeting registrants must: 1. Register and pay all applicable fees. 2. Attend the activity. 3. Complete the Continuing Education Credit Report packet that you received at registration. 4. Initial next to each activity that you attend. PARTIAL CREDIT WILL NOT BE GIVEN FOR ANY ACTIVITY. (For example, if you attended only 1 hour of a 2 hour activity, then you will not get any credit for it.) 5. Complete and sign the form and submit to the registration desk at the end of the conference or after attending your last activity. Include on the form your month of birth in “MM” format (for example, January is “01”) and day of birth in “DD” format (for example, the 3rd of the month is “03”). Also include your NABP e-Profile ID.

Due to ACPE credit recordation requirements, LSHP no longer issues statements of credit. Your CE credit will be recorded by the LSHP office electronically via CPE Monitor (see details below) within 60 days after the meeting.

CPE Monitor is a national, collaborative effort by ACPE and the National Association of Boards of Pharmacy (NABP) to provide an electronic system for pharmacists and pharmacy technicians to track their completed continuing pharmacy education (CPE) credits. All pharmacists and pharmacy technicians must obtain their NABP e-Profile ID by going to www.nabp.net. Your NABP e-Profile ID is required to receive credit for the LSHP Midyear Meeting. After the Midyear Meeting, LSHP will send to NABP and ACPE (via the CPE Monitor) the amount of credit you received (using your e-Profile ID) at the Midyear Meeting. Once this information is received by NABP, pharmacists and pharmacy technicians will be able to log in to access information about their completed CPE.

To receive credit, registrants must attend activities designated for their credentials Activities acceptable for pharmacists are indicated by a “P” suffix in the activity number. Programs acceptable for pharmacy technicians are indicated by a “T” suffix in the activity number.

A total of 8 contact hours (0.80 CEUs) are scheduled for Saturday’s program, of which a maximum of 6 hours (0.6 CEUs) may be earned by an individual participant.

2 Program Saturday, October 27, 2018 Registration 7:00 A.M.—4:00 P.M. Continental Breakfast 7:00—7:45 A.M. Pre-function Area - Level 2 Welcome & Announcements 7:45—8:00 A.M. Meeting Rooms 202/203

Joint Session

8:00—9:00 A.M. Pain Mangement and the Opioid Crisis Brittany Lines, PharmD 0179-0000-18-034-L01-P/0179-0000-18-034-L01-T Meeting Rooms 202/203 9:00—10:00 A.M. A Whole New Monster: Cancer Survivorship Allison Reed, PharmD 0179-0000-18-037-L01-P/0179-0000-18-037-L01-T Meeting Room 202/203

Concurrent Sessions 10:00—11:00 A.M.

In the Hood: <797/800> Edition Hemostatic Agents and Their Uses in Dylan LeBlanc, PharmD Coagulation Disorders 0179-0000-18-039-L04-P/ Logan Murray, PharmD 0179-0000-18-039-L04-T 0179-0000-18-036-L01-P/ Meeting Room 202/203 0179-0000-18-036-L01-T Meeting Room 204

Exhibits 11:00 A.M.—12:00 P.M. Ballroom C&D

Lunch 12:00—1:00 P.M. Ballroom C&D

3 Program continued on next page. Program (continued)

Joint Session 1:00—2:00 P.M. Pharmacy Legislative and Administrative Update Jeffery Evans, PharmD 0179-0000-18-033-L03-P/0179-0000-18-033-L03-T Meeting Rooms 202/203

Concurrent Sessions 2:00—3:00 P.M.

Current Trends and Topics in Diabetes Are you ready? Disaster Preparedness and Management Response for the Pharmacy Team Jamie Terrell, PharmD Jennifer Smith, PharmD, BCPS 0179-0000-18-038-L01-P 0179-0000-18-040-L04-P/ Meeting Rooms 202/203 0179-0000-18-040-L04-T Meeting Room 204

Joint Sessions 3:00—4:00 P.M.

"Put it in Reverse!": Strategies for Reversal of Anticoagulants Molli Gremillion, PharmD 0179-0000-18-031-L01-P/0179-0000-18-031-L01-T Meeting Rooms 202/203

4 Sponsors The success of LSHP’s Midyear Meeting depends, in large part, on the participation and support of pharmaceutical and related interests. LSHP is very appreciative of the companies listed below that have generously supported the 2018 Midyear Meeting by educational or event sponsorship.

Exhibitors Below are the companies who are exhibiting this year. Please be sure to visit their exhibit table and thank them for supporting LSHP.

Achaogen CSL Behring Daiichi Sankyo Helmer Scientific Leadiant Bioscience Morris & Dickson Co Octapharma PharMEDium Services, LLC.

Thank you!!

5 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

8:00—9:00 a.m. Pain Management and the Opioid Crisis

Brittany Lines, PharmD Doctor of Pharmacy Wayne State University College of Pharmacy and Health Sciences Detroit, Michigan

0179-0000-18-034-L01-P/ 0179-0000-18-034-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacist Technician 1. Recognize the roles of different healthcare 1. Identify medications that are high risk for professionals who participate in pain abuse. management. 2. Define good faith dispensing and recognize 2. Define patients that are at high risk for fraudulent prescriptions. abusing opioid medications. 3. Recognize aberrant drug related behaviors. 3. Evaluate the appropriateness of opioid pain medication prescriptions and the potential for over prescribing. 4. Describe actions that pharmacists and/or pharmacy technicians can perform to avoid over prescribing of opioid pain medications.

Dr. Lines has disclosed that he has no relevant financial relationships.

6 DISCLOSURE PAIN MANAGEMENT AND THE OPIOID CRISIS

BRITTANY LINES PHARM.D. UNIVERSITY HEALTH PHARMACY RESIDENT OCTOBER 27, 2018

I have no conflicts of interest, financial, or nonfinancial relationships to disclose to the audience

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PHARMACIST OBJECTIVES TECHNICIAN OBJECTIVES

 Recognize the roles of different healthcare professionals who participate in pain management  Identify medications that are at high risk for abuse  Evaluate the appropriateness of opioid pain medication prescriptions  Define good faith dispensing and recognize fraudulent prescriptions  Describe actions pharmacists and/or pharmacy technicians can perform to avoid over  Recognize and identify aberrant drug related behaviors prescribing of opioid pain medications  Identify patients that are at high risk for abusing opioid medications

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WHAT IS PAIN? WHAT IS PAIN?

AVERAGE NUMBER OF WORK HOURS LOSS BECAUSE OF PAIN Model 1 Model 2 Model 3 204.27 85.74 64.43 45.48 44.45 30.33 30.06 28.73 15.28 14.03 7.8 5 7.58 6

MODERATE PAIN SEVERE PAIN JOINT PAIN ARTHRITIS

Gaskin, et al. “The Economic Costs of Pain in the United States,” 2011. Gaskin, et al. “The Economic Costs of Pain in the United States,” 2011.

7 WHAT IS PAIN? CLASSIFICATION OF PAIN TOTAL INCREMENTAL COSTS OF NUMBER OF HOURS OF WORK MISSED BECAUSE OF PAIN •Short duration Series 1 Series 2 Series 3 • Healing takes days but does not exceed 6 months Acute • Tissue damage that is usually from an identifiable cause 37,472

• Persists for more than 6 months

27,939 • May or may not be associated with an illness Chronic • Develops when a healing process is incomplete 20,530 20,090 19,750 •Somatic Nociceptive • Visceral 11,380 5,550 5,472 5,422 5,296 • Complex, Chronic 2,846 2,618 Neuropathic • Nerve fibers themselves might be damaged, dysfunctional, 7 or injured 8 MODERATE PAIN SEVERE PAIN JOINT PAIN ARTHRITIS

Gaskin, et al. “The Economic Costs of Pain in the United States,” 2011. Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

PATHOPHYSIOLOGY OF NOCICEPTIVE PAIN PATHOPHYSIOLOGY OF NEUROPATHIC PAIN

 Arises from a lesion or disease affecting the somatosensory system.

 Peripheral

 Central

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Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014. Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014. Woolf and Mannion.Lancet 1999; 353;1959-64

ASSESSMENT OF PAIN

 P: provocative and palliative or aggravating factors  Q: quality  R: region or location, radiation  S: severity and other symptoms  T: timing TREATMENT OF PAIN  U: understanding  Critical Care Pain Observation Tool

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Pain and Pain Management. (2015, March 07). Retrieved from https://clinicalgate.com/pain-and-pain- management-2/#bib42

8 TREATMENT OF PAIN : NONPHARMACOLOGIC TREATMENT OF PAIN: TOPICAL AGENTS

Physical Manipulation Massage Cognitive Behavior Therapy  OTC Options

•Chiropractors •Physical  Lidocaine 4% patches Therapists  Capsaicin 0.025% and 0.075%  Methyl salicylate (BenGay, Icy Hot)  Rx Options Acupuncture Relaxation  Capsaicin 8% (Qutenza)  Lidocaine 5% patches

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Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

TREATMENT OF PAIN: NON-OPIOID MEDICATIONS TREATMENT OF PAIN: NON-OPIOID MEDICATIONS

 NSAIDs  Non-selective

 Acetaminophen (Tylenol)  Ibuprofen (IV,PO)  Analgesic  Ketorolac (IV, IM, PO)  Naproxen  Antipyretic  Selective  Formulations: IV, PO, Rectal formulations  Diclofenac (PO, Topical)  Celecoxib  Meloxicam  Aspirin – Salicylate

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Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014. Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

TREATMENT OF PAIN: GABA ANALOGUES TREATMENT OF PAIN: MUSCLE RELAXERS

Analgesic •Baclofen (PO, Intrathecal) • Indicated for the management of • Cyclobenzaprine Gabapentin postherpetic neuralgia in adults Effects • Tizanidine

• Approved for fibromyalgia, Sedative • Carisoprodol Pregabalin postherpetic neuralgia, Effects •Methocarbamol (IV, IM, PO) neuropathic pain

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Baclofen. Package Insert Cyclobenzaprine. Package Insert Gabapentin. Package Insert Tizanidine. Package Insert Pregabalin. Package Insert Carisoprodol. Package Insert Methocarbamol. Package Insert

9 TREATMENT OF PAIN: ANTIDEPRESSANTS TREATMENT OF PAIN: OPIOIDS

Opioid Receptors Effect • Tricyclic antidepressant Mu Euphoria, supraspinal analgesia, confusion, dizziness, Amitriptyline • NE an 5HT reuptake inhibitor, also block nausea, respiratory depression, miosis acetylcholine and histamine receptors Delta Spinal analgesia, cardiovascular depression, decreased brain and myocardial oxygen demand

• Serotoninergic and Norephedrine Kappa Spinal analgesia, dysphoria, psychomimetic effects, Duloxetine reuptake inhibitor feedback inhibition of endorphin system

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Amitriptyline. Package Insert Duloxetine. Package Insert https://www.pharmacytimes.com/publications/issue/2011/june2011/an-overview-of-opioids

TREATMENT OF PAIN: OPIOIDS SIDE EFFECTS OF OPIOID THERAPY

 Strong Agonists  Mild to Moderate Agonists Effect Treatment Options  Morphine* (IV, IM, Rectal, PO)  Codeine Pruritis Anti-histamines  Hydromorphone (IV, IM, SC, PO)  Oxycodone*

 Oxymorphone (IM, IV, SC, PO)  Hydrocodone Constipation Stimulant Laxative  Methadone (IM, SC, PO)  Tramadol PAMORAs  Fentanyl (IV, Transdermal, Sublingual)

 Meperidine* (IV, IM, PO) Nausea 5HT3 Antagonist

PAMORA: Peripherally acting mu-opiod antagonists 21 22

* Indicates renal dose adjustments are indicated

Pathan H, Williams J. Basic opioid pharmacology: an update. British Journal of Pain. 2012 Baumann TJ, Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

POTENTIAL SHORT TERM EFFECTS OF OPIOID THERAPY RISKS OF OPIOIDS IN MANAGING PAIN

CNS depression Physical To l e r a n c e Addiction Dependence • Euphoria •Higher dose • Body relies •Strong desire Respiratory Depression is needed to on a external or produce the source of compulsion • Starting the medication same effect opioids to to take the • Increasing the dose prevent drug despite withdrawal harm 23 24

Pathan H, Williams J. Basic opioid pharmacology: an update. British Journal of Pain. 2012 http://www.naabt.org/addiction_physical-dependence.cfm

10 ASSESSMENT QUESTION 1:

 What healthcare professionals are involved in pain management? A. Physical Therapist B. Physician C. Pharmacist D. All of the Above

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ASSESSMENT QUESTION 1: ASSESSMENT QUESTION 2

 For a patient that is opioid naïve what would be the most appropriate agent to use?  What healthcare professionals are involved in pain management? A. Morphine A. Physical Therapist B. Fentanyl B. Physician C. Hydromorphone C. Pharmacist D. Hydrocodone D. All of the Above

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ASSESSMENT QUESTION 2

 For a patient that is opioid naïve what would be the most appropriate agent to use? A. Morphine B. Fentanyl C. Hydromorphone D. Hydrocodone PAIN MANAGEMENT GUIDELINES

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11 ROLE OF OPIOIDS IN PAIN MANAGEMENT CDC GUIDELINE FOR PRESCRIBING OPIOIDS FOR CHRONIC PAIN

 Goal: Ensure safe and more effective treatment, improve patient  CDC Guideline for Prescribing Opioids for Chronic Pain outcomes, reduce opioid use disorders  March 2016 When to initiate Opioid selection, Assessing risk and  The Joint Commission or continue dosage, duration, addressing harms opioids for follow-up, and  July 2017 of opioid use chronic pain discontinuation

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Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016;65(No. RR- Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. 1):1–49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1 MMWR Recomm Rep 2016;65(No. RR-1):1–49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1. https://www.jointcommission.org/assets/1/18/Joint_Commission_Enhances_Pain_Assessment_and_Management_Requirements_for_Accredited_Hospitals1.P DF

THE JOINT COMMISSION THE JOINT COMMISSION

 Standard LD.04.03.13  Standard MS.05.01.01  Pain assessment and pain management, including safe opioid prescribing, is identified as an organizational priority for the hospital.  The medical staff is actively involved in pain assessment, pain management and safe opioid prescribing through the following  Standard PC.01.02.07  Participating in the establishment of protocols and quality metrics  The hospital assesses and manages the patient’s pain and minimizes the risks associated with treatment.  Reviewing performance improvement data

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Sandlin, D. (2000). The new joint commission accrediation of healthcare organizations requirements for pain assessment and Sandlin, D. (2000). The new joint commission accrediation of healthcare organizations requirements for pain assessment and treatment: A pain in the assessment? Journal of PeriAnesthesia Nursing, 15(3), 182-184. doi:10.1053/jpan.2000.7511 treatment: A pain in the assessment? Journal of PeriAnesthesia Nursing, 15(3), 182-184. doi:10.1053/jpan.2000.7511

THE JOINT COMMISSION ROLE OF A PHARMACIST IN MANAGING PAIN

 Alternative Therapy Options  Standard PI.01.01.01  De-escalation/escalation of care  The hospital collects data on pain assessment and pain management including  Symptom Analysis types of interventions and effectiveness.  Acute vs chronic  Standard PI. 02.01.01  Timing of onset  The hospital analyzes data collected on pain assessment and pain management to identify areas that need change to increase safety and quality for patients.  Precipitating factors  Location  Activities that make it worse? better? 35  Impact on daily activities 36

Sandlin, D. (2000). The new joint commission accrediation of healthcare organizations requirements for pain assessment and treatment: A pain in the assessment? Journal of PeriAnesthesia Nursing, 15(3), 182-184. doi:10.1053/jpan.2000.7511 Tanzi, M., PharmD. (2015, September 1). Pain management 101 for pharmacists. Retrieved September 2, 2018,

12 PHARMACIST IMPACT IN PAIN MANAGEMENT PHARMACIST IMPACT ON PAIN MANAGEMENT Opioid Kaweah Delta Medical Stewardship Center in Visalia California  Opioid Stewardship Program Program  Pharmacist lead at Penobscot Community Health Care Optimization Acceptance rate of the  Informed consent, acknowledging the risks of Pain pharmacist recommendations  Annual contract for random urine drug test = 88% Management  Provide recommendations  Patients receiving chronic opioids decrease by 62.7% from October 2013 to March Opioid Indirect cost avoidance = Stewardship 2017 program $2.7 Million 37 38

P. (2018, January 25). Pharmacist Involvement in Opioid Stewardship and its Impact in a Small Community Health System. Retrieved September 2, 2018, from Erickson, A., MA. (2015, June 1). Knocking out pain: Hospital pharmacists launch new approach to pain management. Retrieved https://www.pharmacy.umn.edu/degrees-and-programs/postgraduate-pharmacy-residency-program/news-events-and-publications/curbside-consult-volume-15-issue-5-fourth-quarter- September 2, 2018, from https://www.pharmacist.com/article/knocking-out-pain-hospital-pharmacists-launch-new-approach-pain- 2017/pharmacist-involvement-opioid-stewardship-and-its-impact-small-community-health management

ASSESSMENT QUESTION 3: ASSESSMENT QUESTION 3:

 The CDC Guideline for prescribing opioids for chronic pain include all of the  The CDC Guideline for prescribing opioids for chronic pain include all of the following EXCEPT following EXCEPT A. When to initiate or continue opioids for chronic pain A. When to initiate or continue opioids for chronic pain B. Opioid selection, dosage, duration, follow-up, and discontinuation B. Opioid selection, dosage, duration, follow-up, and discontinuation C. Assessing risk and addressing harms of opioid use C. Assessing risk and addressing harms of opioid use D. The medical staff is actively involved participating in the establishment of protocols D. The medical staff is actively involved participating in the establishment and quality metrics of protocols and quality metrics

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OPIOID CRISIS AND OVER-UTILIZATION

OPIOID CRISIS

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13 OPIOID CRISIS: DEPARTMENT OF HEALTH AND HUMAN SERVICES OPIOID CRISIS: LOUISIANA STATISTICS

 5 Priorities to Combat with Opioid Epidemic  Improving access to treatment and recovery services  Promoting use of overdose-reversing drugs  Strengthening our understanding of the epidemic through better public health surveillance  Providing support for cutting edge research on pain and addiction  Advancing better practices for pain management

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Price, T. E., MD. (2018, March 08). Secretary Price Announces HHS Strategy for Fighting Opioid Crisis. Retrieved September 2, 2018, from https://www.hhs.gov/about/leadership/secretary/speeches/2017- speeches/secretary-price-announces-hhs-strategy-for-fighting-opioid-crisis/index.html https://www.drugabuse.gov/drugs-abuse/opioids/opioid-summaries-by-state/louisiana-opioid-summary

OPIOID CRISIS: LOUISIANA LAWS OPIOID CRISIS: LOUISIANA LAW

 Prohibits a medical practitioner from prescribing more than a seven-day supply when issuing a first time opioid prescription for outpatient use to an adult  New law expands the mandate to access the Prescription Monitoring Program patient with an acute condition. (PMP) program prior to initially prescribing any opioid and if the patient's course of  Requires a medical practitioner to do both of the following prior to issuing a treatment continues for more than 90 days. prescription for an opioid:

 Consult with the patient regarding the quantity of the opioid and the  New law requires all prescribers of controlled dangerous substances (CDS) in patient's option to fill the prescription in a lesser quantity. Louisiana to obtain three continuing education credit hours as a prerequisite of  Inform the patient of the risks associated with the opioid prescribed. license renewal in the first annual renewal cycle after Jan. 1, 2018. CME

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http://www.lsbme.la.gov/content/opioid-prescribing-laws-recent-changes http://www.lsbme.la.gov/content/opioid-prescribing-laws-recent-changes

LOUISIANA PRESCRIPTION MONITORING PROGRAM (PMP)

 Operated by the Louisiana Board of Pharmacy, the PMP is an electronic system that monitors controlled substances.

 They receive the transaction reports from all the dispensers, house the data on servers owned by the Board, and host the web portal for authorized direct access users.

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http://www.pharmacy.la.gov/index.cfm?md=pagebuilder&tmp=home&pid=5

14 ABERRANT DRUG-RELATED BEHAVIOR IDENTIFYING HIGH RISK PATIENTS

Author Instrument n Follow up End Point Sensitivity Specificity (Year) Duration  Akbik Screener and 397 Duration unclear Urine toxicology 0.68 0.39 Behaviors that potentially indicate misuse of the prescribed opioid, or even addiction (2006) Opioid (155 had screen showing (0.52 – 0.81) for (0.29 – 0.49) Assessment for urine illicit substances SOAPP Version 1 SOAPP Version 1  Stealing or borrowing opioid medications Patients with toxicology and/or score > 8 score > 8 Pain (SOAPP) results) unprescribed  Patient – initiated dose escalation Version 1 opioids  Concurrent use of an illicit substance Bulter Revised 283 5 months Positive result on 0.80 0.68 (2008) Screener and 223 completed 5 the aberrant drug (0.7 – 0.89) for (0.6 – 0.75) for  Diversion Opioid month follow up behavior index SOAPP-R score > SOAPP-R score > Assessment for 18. 18 Patients with Pain (SOAPP-R)

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Merlin, J. S., et a;. (2014). Aberrant Drug-Related Behaviors: A Qualitative Analysis of Medical Record Documentation in Patients Referred to an HIV/Chronic Pain Clinic. Pain Medicine, 15(10), Chou, et al. The Journal of Pain. (10). 131 – 146

ASSESSMENT QUESTION 4: ASSESSMENT QUESTION 4:

 What are tools to identify high risk patients for abusing opioid medications?  What are tools to identify high risk patients for abusing opioid medications? A. Using the Prescription Monitoring Program to verify appropriateness of A. Using the Prescription Monitoring Program to verify appropriateness of prescription prescription B. Use different questionnaires (SOAP Version 1, SOAP-R) to assess their drug- B. Use different questionnaires (SOAP Version 1, SOAP-R) to assess their drug- related behaviors related behaviors C. Evaluate prior medical history associated with drug addictions, family history, etc. C. Evaluate prior medical history associated with drug addictions, family history, etc. D. All of the above D. All of the above

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OPIOID OVERDOSE

 Use of Prescription Drug Monitoring Programs and recognition of aberrant drug seeking behaviors  How to prevent and manage opioid overdose OPIOID OVERDOSE AND ADDICTION TREATMENT  Ensure access to treatment for patients addicted to opioids  Encourage the public to call 911

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15 OVERDOSE TREATMENT: NALOXONE NALOXONE STANDING ORDER IN LOUISIANA  LA. R.S 40.978.2  A licensed medical practitioner may, directly or by standing order,  Opioid Antagonist prescribe or dispense the drug Naloxone or another opioid antagonist without having examined the individual to whom it  Used for Opioid Overdose may be administered if two conditions are met  Will cause acute withdrawal  The licensed medical practitioner must provide the individual  Pain receiving and administering the naloxone or other opioid antagonist all training required by the Louisiana Department of  Anxiety Health for the safe and proper administration  Tachypnea  Naloxone or other opioid antagonist must be prescribed or dispensed in such a manner that it shall be administered 55 through a device approved for this purpose 56

Naloxone. Package Insert

ADDICTION TREATMENT: BUPRENORPHINE ADDICTION TREATMENT: METHADONE

 Buprenorphine  Synthetic opioid  Partial mu – opioid agonist  Naloxone  Used for treatment of addiction and chronic pain  Opioid antagonist  Suboxone = Buprenorphine / Naloxone  Center for Substance Abuse Treatment  Part of the US Department of Health and Human Services

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Suboxone. Package Insert. Subutex. Package Insert.

REVIEW: METHADONE MAINTENANCE SUMMARY: THE ROLE A PHARMACIST

Title Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence Objective Evaluate the effects of methadone maintenance treatment compared with  Understand different analgesics and where they fit into pain management treatments that did not involve opioid replacement therapy for opioid dependence  Explain to providers and patients the severity of the opioid epidemic Methods Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current  Recognize aberrant drug related behaviors Contents, Psychlit, CORK Results • Statistically significantly in treatment and in the suppression of heroin use  Counsel patients and caregivers on the use, storage, and administration of (6 RCTs, RR = 0.66 95% CI 0.56 0.78) naloxone • Not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12 1.25) ‐  Know where available treatment clinics are for patients battling addition • Not statistically different in mortality (4 RCTs, RR=0.48; 95%CI: 0.10 2.39) ‐ Conclusion Methadone is an effective maintenance therapy intervention for the ‐ 59 60 treatment of heroin dependence

Mattick, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews 2009, Issue 3.

16 SUMMARY: THE ROLE A PHARMACY TECHNICIANS PAIN MANAGEMENT AND THE OPIOID CRISIS

BRITTANY LINES PHARM.D. UNIVERSITY HEALTH PHARMACY RESIDENT  Know which analgesics are at high risk for potential abuse and diversion NOVEMBER 27, 2018

 Recognize aberrant drug related behaviors

 Identifying and addressing any discrepancies that are made with control inventory

61 62

17 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

9:00—10:00 a.m. A Whole New Monster: Cancer Survivorship Allison Reed, PharmD

Purdue University, College of Pharmacy, West Lafayette, IN

179-0000-18-037-L01-P/0179-0000-18-037-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: 1. Describe short-term and long-term problems survivors face post-treatment. 2. Utilize the National Comprehensive Cancer Network Patient/Provider Survivorship Assessment. Technicians: 3. Determine non-pharmacologic and 1. Define survivorship. pharmacologic treatments to survivorship 2. Identify resources available for cancer issues. survivors and their loved ones.

Dr. Reed has disclosed that she has no relevant financial relationships.

18 2 Disclosures

 I have nothing to disclose in relation to this presentation.

A Whole New Monster: Cancer Survivorship 1 Allison Reed, Pharm.D. PGY-1 Pharmacy Practice Resident University Health Shreveport

3 Objectives 4 Statistics

 Pharmacist Objectives  Five times more survivors alive today than 45 years ago Describe short-term and long-term problems survivors face during treatment and post-treatment  Common surviving cancer types Utilize the National Comprehensive Cancer Network Patient/Provider Survivorship Assessment  Breast Determine non-pharmacologic and pharmacologic  Prostate treatments to survivorship issues  Colorectal  Technician Objectives Define survivorship Identify resources available for cancer survivors and their loved ones

American Society of Clinical Oncology. What is Survivorship? Available at: www.cancer.net. National Institute of Cancer at the National Institutes of Health. Statistics. Available at: cancercontrol.cancer.gov.

5 American Society of Clinical Oncology 6 National Cancer Institute (NCI) (ASCO) Survivorship Definitions Survivorship Definitions

 Having no signs of cancer after finishing treatment  ”Survivorship focuses on health and life of a person with cancer post treatment until the end of life.”  Living with, through, and beyond cancer  Accounts for physical, psychosocial, and economic  Phases of survivorship problems  Acute  Includes follow-up, secondary issues from treatment, and  Extended quality of life  Permanent

American Society of Clinical Oncology. What is Survivorship? Available at: www.cancer.net. National Cancer Institute at the National Institutes of Health. NCI dictionary of cancer terms. Available at: www.cancer.gov.

19 National Comprehensive Cancer 7 8 Assessment Question #1 Network (NCCN) Survivorship Definition  Which of these is not included in any of the definitions  “An individual is considered a cancer survivor from the discussed today about being a cancer survivor? time of diagnosis through the balance of his or her life.” A.Having been diagnosed with cancer  Most comprehensive definition  Includes multiple aspects of life B. Having no signs of cancer after completing treatment for cancer C.Having been on the show “Survivor” and finishing the season D.After initial treatment is over and the month that follow

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

9 Issues Post-Treatment 10 Recurrence

Recurrence Menopausal Symptoms Cure Sometimes. Secondary Cancer Sexual Dysfunction Treat often. Cardiac Dysfunction Pain Comfort Always. Insomnia Lymphedema Hypersomnia Cognitive Difficulty  Counsel on side effects of new regimen Fatigue Mental Health Issues  Ensure proper supportive care Infertility Financial Health  Support the patient’s decision

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. WiseGeek. What is bronchial pneumonia? Available at: www.wisegeek.com.

11 Secondary Cancer 12 Cardiac Dysfunction

 Risk factors  Anthracyclines and HER-2 therapy  Breast cancer  Dose-dependent and irreversible  Hodgkin’s Lymphoma  Dose-independent and reversible  Anthracyclines  Dexrazoxane for anthracycline-  Alkylating agents induced cardiotoxicity  Common secondary cancers  Goal-directed therapy for heart Leukemia failure  ACE inhibitor, ARB, or ARNI  Beta blocker  Aldosterone antagonist

University of New Mexico. Secondary Malignancies. Available at: cancer.unm.edu. St. Dominic’s. Heart Failure Clinic. www.stdom.com. Ziegler L. The Conversation. Not enough cancer patients are getting end of life care- new study. Available at: www.theconversation.com. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. National Comprehensive Cancer Network. Understanding your risk of developing secondary cancers. Available at: www.nccn.org. Kondapalli L. American College of Cardiology. Cardiotoxicity: an unexpected consequence of HER2-targeted therapies. Available at: www.acc.org.

20 13 Lapatinib Study 14 Insomnia

 Difficulty recovering  Pooled cohort study   3689 patients received lapatinib Non-pharmacologic  Sleep hygiene  62 cardiac events in 60 patients  Pharmacologic  53 patients asymptomatic  Z-hypnotics  Ramelteon  Temazepam  Doxepin  Suvorexant

Taylor M. Lifehacker. Why insomnia happens and what you can do to get better sleep. Available at: www.lifehacker.com. Perez EA, et al. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc 2008; 83(6): 679-686. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

15 Hypersomnia 16 Fatigue  Nonspecific causes  Nonspecific causes  Insufficient sleep time  Returning to normal schedule while prioritizing tasks  Sleep hygiene  Pharmacists’ role  Too much sleep  Non-pharmacologic  >9 hours per night Physical activity  Refer Therapy Sleep hygiene  Pharmacologic Last line Methylphenidate

Matt Duffin. Youtube. Living and Sleeping with Idiopathic Hypersomnia Available at: www.youtube.com. Endometriosis Foundation of America. Endometriosis symptoms: fatigue & personality changes. Available at: www.endofound.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

17 Infertility 18 Menopausal Symptoms

 Risk factors: chemotherapy, radiation  Causes: hormone modulators  Educate on sperm banking/egg harvesting  Tamoxifen   Educate on delaying treatment Leuprolide  Aromatase inhibitors  Keep goals in mind  Bicalutamide

Livestrong. Cancer and fertility risks for men. Available at: www.livestrong.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Ameya C. Stylecraze. 7 effective yoga pases to treat menopause. Available at: www.stylecraze.com. Check Ovulation. Living with infertility: “one more shot”. Available at: www.checkovulation.com. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

21 19 20 Treatment of Menopausal Symptoms Vasomotor Symptoms Female Male First-line Non-pharmacologic Non-pharmacologic management such as management such as • Acupuncture • Acupuncture • Yoga • Yoga • Exercise • Exercise Second-line Non-hormonal treatment If he is on androgen-deprivation such as therapy, reduce dose. • Low dose antidepressants If not, hormonal therapy such as • Anticonvulsants • Medroxyprogesterone • Cyprotereone acetate • Estrogens Third-line Hormonal therapy Non-hormonal therapy • Oral, transdermal, ring, • Only venlafaxine & gabapentin etc. • Estrogens/bazedoxifene

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Chemocare. Menopause & chemotherapy. Available at: chemocare.com.

21 Non-Hormonal Treatment of Vasomotor 22 Vaginal Dryness and Gynecomastia Symptoms Treatment

Vaginal dryness  Gynecomastia Vaginal moisturizers, gels, etc.  Prophylactic radiation Topical vitamin D or E  Tamoxifen Lubricants for sexual activity  Reduction Hormonal treatments mammoplasty Local estrogen such as rings, suppositories, or creams Testosterone or DHEA

Treatment of Sexual Dysfunction in 23 Sexual Dysfunction 24 Women  Potential Causes  Pain with sex  Ospemifene  Endocrine therapy  Vaginal moisturizers or oils  Selective estrogen receptor  Radiation  Vaginal dilators modulator  Surgery  Ospemifene  Contraindications  Androgen-deprivation therapy  DHEA  Effect on Survivor  Topical anesthetics  Stress  Pelvic physical therapy  Tension in relationships  Insecurity

Chain Drug Review. Duchesnay acquires osphena u.s. rights from shionogi. Available at: www.chaindrugreview.com.. Ospemifene. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

22 Treatment of Sexual Dysfunction in Treatment of Sexual Dysfunction in 25 26 Women Men  Orgasms with less  Assess total morning testosterone intensity/difficulty achieving  Exception: prostate cancer  Vibrators/clitoral stimulatory devices  Erectile dysfunction  Pelvic physical therapy  PDE5 inhibitors  Lack of desire/intimacy  Lifestyle modifications  Androgens  Flibanserin  Anxiety/depression  Bupropion Mixed-5HT1a  Ejaculation issues  Buspirone agonist/5HT2a antagonist  Psychological evaluation  Flibanserin Hyposexual  SSRI premenopausal women  Multiple issues or refractory:  Clomipramine refer Drug interactions Flibanserin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Sprout Pharmaceuticals. Addyi. Available at: www.addyi.com.  Pelvic physical therapy Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Thibault O. Medical X Press. Viagra turns 20: chronicle of a global success. Available at: www.medicalxpress.com.

27 Treatment of Sexual Dysfunction in 28 Pain Men  Potential Causes  Less intense orgasms/difficulty orgasming  Treatment-related  PDE5 inhibitors  Recurrence  Vibration therapy  General Principles of Treatment  Pelvic physical therapy  Always include non-pharmacologic  Low desire/intimacy  Best to use non-opioids whenever  Refer to psychology possible  Multiple issues/refractory: refer  Use opioids at the lowest dose for the shortest amount of time

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Cares K. Essential Oils for Health News. Top essential oils for pain relief. Available at: www.essentialoilsforhealth.news.

29 Treatment of Pain 30 Treatment of Pain  Neuropathic Pain  Tissue Pain  Gabapentin  Treat the same as muscle and joint pain  Duloxetine  Can add ultrasonic stimulation Other options: opioids, topical patches, creams  GI/Urinary/Pelvic Pain  Amputation or dissection  Hydration  Physical therapy, massage  Refer  Nerve blocks, trigger point injections  Post-Radiation Pain  Muscle and Joint Pain  Physical therapy  Typical pain management  Treat the etiology  Skeletal Pain  Treat the same as muscle and joint pain  Can add bisphosphonates

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org..

23 31 Lymphedema 32 Treatment of Lymphedema

 Increases risk  Effect on Survivor  Obesity  Pain  Large number of lymph nodes  Decreased range of motion removed  Skin tightness  Site of surgery or radiation  Treatment and Our Role  Stage 0 & 1  reversible  Monitor and treat for infections  Stage 2 & 3  irreversible  Sizing for compression garments  Physical therapy

Mayo Clinic. Lymphedema. Available at: www.mayoclinic.org. Mayo Clinic. Lymphedema. Available at: www.mayoclinic.org. MD Anderson. Lymphedema prevention and treatment. Available at: www.mdanderson.org. MD Anderson. Lymphedema prevention and treatment. Available at: www.mdanderson.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

33 Cognitive Difficulty 34 Mental Health Issues  Chemo brain  General Anxiety Disorder, Depression, Social Anxiety, etc.  Can be caused by emotional stress, pain, etc.  Potential Causes  Effect on Survivor  Difficulty interacting with loved ones  Our Role as Pharmacists  Effects on Survivor  Recognize  Feeling of isolation  Treat underlying cause  How Can Pharmacists Help?  Methylphenidate  Notice small changes  Modafinil  Find the therapy that fits best for our patient  SSRI or SNRI  Drug interactions with cancer treatment

BBC Future. Brain. Available at: www.bbc.com. Skinny News. Can exercise make your brain grow bigger? Available at: www.skinnynews.com. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org. Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

35 Financial Problems 36 Assessment Question #2

 Cost of Treatment and Follow Up Care  JD is a 54 year old female who just finished treatment for a HER-2 -, ER+/PR+ stage II breast cancer. She notices  Effects on Survivor and Survivorship that she is increasingly tired every day after she gets  Guilt home from work. She used to garden after work, but  Choice of treatment now it is all she can do to finish her eight hours at her accounting firm. What survivorship issue does JD face  How Can Pharmacists Help? A) Financial problems  Finding ways to decrease cost of care  Find patient assistance programs B) Cognitive difficulty  Help with paperwork C) Lymphedema D) Fatigue E) Hypersomnia

Banegas MP, et al.. Health Aff (Millwood) 2016; 35(1): 54-61. Kiernan JS. Wallethub. The best way to pay off debt; which debt to pay first & more. Available at: www.wallethub.com.

24 National Comprehensive Cancer Network 37 Assessment Question #3 38 Patient Survivorship Assessment  What should JD NOT do to help alleviate her fatigue? A)Exercise vigorously for 150 minutes every week B) Set realistic expectations for herself C)Treat underlying causes of fatigue D)Prioritize her tasks E) Practice sleep hygiene

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

National Comprehensive Cancer 39 40 Assessment Question #4 Network Provider Survivorship Key  Which of these is not assessed on the NCCN Patient Survivorship Assessment? A)Cognitive Function B) Financial Problems C)Healthy Lifestyle D)Immunizations and Infections

Denlinger CS, et al. National Comprehensive Cancer Network. Survivorship. Available at: www.nccn.org.

41 Resources for Survivors 42 Resources for Loved Ones  ASCO resources  American Cancer Society  American Cancer Society

American Society of Clinical Oncology. Survivorship resources. Available at: www.cancer.net. American Cancer Society. Survivorship: During and After Treatment. Available at: www.cancer.org. Wolf M. Cancer survivorship 1uote #11. Available at: www.cancer-companions.org. American Cancer Society. Interactive Caregiver Resource Guide. Available at: www.cancer.org.

25 43 Think, Pair, Share 44 Questions

 As a health system pharmacist, what ways do you think you will utilize the most to help cancer survivors?

A Whole New Monster: Cancer Survivorship 45 Allison Reed, Pharm.D. PGY-1 Pharmacy Practice Resident University Health Shreveport

26 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

10:00—11:00 a.m. In the Hood: <797/800> Edition

Dylan LeBlanc, PharmD Emergency Medicine/ Critical Care Pharmacy Specialist Ochsner LSU Health Shreveport, LA

0179-0000-18-039-L04-P/0179-0000-18-039-L04-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: Technicians: 1. Identify the different microbial 1. Identify the different microbial contamination risk levels associated with contamination risk levels associated with compounded sterile preparations (CSP). compounded sterile preparations (CSP). 2. Determine the beyond use date (BUD) for 2. Determine the beyond use date (BUD) for CSPs CSPs 3. Outline the proper personal protective 3. Outline the proper personal protective equipment (PPE) procedure. equipment (PPE) procedure. 4. Explain USP <800> requirements. 4. Explain USP <800> requirements.

Dr. LeBlanc has disclosed that he has no relevant financial relationships.

27 Disclosure

In the Hood: • The presenter has nothing to disclose in relation to this <797/800> Edition presentation Dylan J. LeBlanc, Pharm.D. Clinical Pharmacist University Health | Shreveport

1 2

Pharmacist and Technician Poll Objectives

• Who here has ever had to compound a medication for a • Identify the different microbial contamination risk levels patient in a hospital? associated with compounded sterile preparations (CSP) • Determine the Beyond Use Date (BUD) for CSPs • Outline the proper personal protective equipment (PPE) procedure • Explain USP <800> requirements

3 4

Sterile Compounding

Otherwise Combining Admixing altering a drug

Sterile USP Chapter <797> Compounding Repackaging Diluting Sterile Compounding

Reconstituting Pooling 5 6

28 CSP Risk Levels and Examples Beyond Use Dating

•Sterile ingredients BUD •Involves not more than 3 commercially manufactured packages • RT: 48 hours Low Medium High Immediate Use •No more than 2 entries into any 1 sterile container or device Low • Fridge: 14 days •Compounding areas: ISO 5 PEC, ISO 7 buffer area, ISO 7 ante area (HD), ISO 8 ante area (non‐HD) • Frozen: 45 days

BUD Batch •Sterile ingredients SDV of PCA from non‐ preparation of •Involves more than 3 commercially manufactured products • RT: 30 hours levetiracetam to sterile powder Medium •Compounding areas: ISO 5 PEC, ISO 7 buffer area, ISO 7 ante area (HD), ISO 8 ante area • Fridge: 9 days vancomycin 1250 (non‐HD) make a IVPB for a ingredients Preparing a • Frozen: 45 days mg in 250 mL patient D5W norepinephrine BUD drip at the •Non‐sterile ingredients • RT: 24 hours bedside for a High •Compounding areas: ISO 5 PEC, ISO 7 buffer room, ISO 7 ante area (HD), ISO 8 ante area (non‐HD) • Fridge: 3 days patient that is • Frozen: 45 days Total parenteral post cardiac arrest nutrition (TPN) •Intended for emergency situations that involve compounding in a non‐ Immediate sterile environment AND administration must begin within 1 hour of Begin administration preparation within 1 hour Use •Compounding areas: non‐sterile environment, i.e., regular air 7 8

Multi‐Dose Vials (MDV) vs Bag‐Vial Combinations Single‐Dose Vials (SDV)

MDV BUD SDV BUD • Add‐Vantage®, Mini‐Bag Plus®, Add‐A‐Vial System® • Up to 28 days* • Outside of ISO Class 5 environment • Why (?) • May be prepared outside of ISO Class 5 environment • 1 hour* • BUD: provided by the manufacturer • Inside of ISO Class 5 environment • 6 hours*

*Unless manufacturer specifies sooner 9 10

Assessment Question #1 Assessment Question #2

• When preparing a batch of norepinephrine in a ISO Class • Based upon your assessment of batched norepinephrine 5 environment, what is the CSP risk level of the final in the previous answer, what is the CSP’s maximum BUD? preparation?

11 12

29 Personal Protective Equipment Environmental Control (PPE)

Shoe covers, Remove Enter Apply hair Hand Sterile • Cleaning • Walls personal Gown clean antiseptic cover, hygiene gloves items room hand gel • Hood • Ceilings face •Counters •Storage shelves mask

Daily • Floors • Monitoring • Temperature Monthly Dirtiest ---> Cleanest •Air pressure

13 14

Personnel Assessment

•Air sampling •Competency •Gloved fingertip test, •Gloved fingertip test, media fill test (HD) media fill test (Non‐HD) •Aseptic technique USP Chapter <800> Annual Annual •Garbing and gowning Hazardous Medications

‐ technique Bi

15 16

Goals Hazardous Drugs

• National Institute for Occupational Safety and Health (NIOSH) HD list Environmental Patient safety Worker safety • Reviewed every 12 months protection • Risk assessment

17 18

30 What is a HD? Assessment Question #3

• What are the three goals of USP Chapter <800>, Antineoplastics Non‐ Reproductive Hazardous Medications? antineoplastics risk

19 20

Hood Requirements Assessment Question #4

• Negative pressure room • Externally vented • Compounding • What is the correct order that the hazardous medications • Deactivated & decontaminated  cleaned  disinfected hood must be cleaned at least daily? • Plastic backed preparation mat • Closed system transfer devices • Continuous power

21 22

Personnel Handling HD Facility Requirements Responsibilities

• Designated areas • Unpacking Prevent harm Minimize • Storage to patients exposure • Sterile vs. non‐sterile compounding • Dispensing • Administering • Environmental control at least every 6 months • No studies or standards for surface contamination Minimize • Training offered to personnel responsible contamination

23 24

31 PPE Requirements

Head, Hair, Gloves Gowns Shoe, Sleeve Covers

Eye and Face Respiratory Disposal Protection Protection With your Game Show Host: Dylan LeBlanc

25 26

CSP Risk PPE - $100 PPE BUD USP 800 Lagniappe Levels  True or False – When compounding hazardous $100 $100 $100 $100 $100 medications, personnel should wear 2 pairs of gloves and 2 pairs of gowns. $200 $200 $200 $200 $200

$300 $300 $300 $300 $300

$400 $400 $400 $400 $400

$500 $500 $500 $500 $500

Final Jeopardy 27 28

PPE - $200 PPE - $300

 What type of gown should be worn when  How frequently should a gown be changed if I compounding non-hazardous medications? am compounding hazardous medications?

29 30

32 PPE - $400 PPE - $500

 What type of gown must be worn when  Outline the proper technique required before compounding hazardous medications? entering the buffer area to compound a non- hazardous CSP.

31 32

CSP Risk Level - $100 CSP Risk Level - $200

 What type of risk level is associated with  Give an example of a medication with a Medium compounding non-sterile medications? CSP risk level

33 34

CSP Risk Level - $300 CSP Risk Level - $800

 What medications are associated with a low CSP  Today, I am working in a Pediatric Satellite. I risk level? receive an order from Dr. JG for Baby Boy-BG. The order is for total parenteral nutrition to start this evening. After verification, what risk level will the preparation be and why?

35 36

33 CSP Risk Level - $500 BUD - $100

 What CSP risk level(s) involve sterile ingredients  Why are MDV’s typically dated with a beyond only? use date for 28 days, unless the manufacturer specifies sooner?

37 38

BUD - $200 BUD - $300

 Today, I am working in the MICU satellite. While  A CSP with a low risk level is good for how long on rounds, a patient starts to code. The primary in the freezer? team requests that the pharmacist attending make a norepinephrine drip at the bedside. How long does this medication have to be administered?

39 40

BUD - $400 BUD - $500

 Assuming that I am working in an IV room that  Give an example of a device system that does is compliant with USP 797, I decide that I will not need to follow USP 797 rules for BUD. make a batch of Vancomycin 1000 mg / D5W 250 mL. How long of a BUD should be assigned to this medication if I store it in a refrigerated environment?

41 42

34 USP 800 - $100 USP 800 - $200

 Personnel should be trained how often if they  How many sets of gloves are required when will be compounding hazardous medications? unpacking hazardous medications?

43 44

USP 800 - $300 USP 800 - $400

 What device system must be used when  Deactivation of the hood should occur using administering medications to patients? which liquid?

45 46

USP 800 - $500 Lagniappe - $100

 Why must powder free gloves be worn when  How frequently should the hood be cleaned? compounding hazardous medications?

47 48

35 Lagniappe - $200 Lagniappe - $300

 True/False – I can bring cardboard boxes and  How long are single dose vials good for inside unpackage them in sterile areas. of an ISO Class 5 environment?

49 50

Lagniappe - $400 Lagniappe - $500

 I am working in the buffer room to compound a  What type of material should the floors be chemotherapy medication for patient JS. I notice cleaned with? after I am finished, that there is liquid oozing on my hands. What should I do?

51 52

Final Jeopardy References  What material should be referred to whenever there is a hazardous medication that has been spilled in order to see how to most appropriately USP Chapter 797, Pharmaceutical Compounding, Sterile manage the situation? Preparations ASHP Guidelines on Compounding Sterile Preparations – Am J Health Syst Pharm. 2014;71(2):145‐166. USP Chapter 800, Hazardous Drugs, Handling in Healthcare Settings American Society of Health‐System Pharmacist. ASHP guidelines on handling hazardous drugs. Am J Health‐Syst Pharm. 2006; 63:1172‐93.

54 53

36 In the Hood: <797/800> Edition Dylan J. LeBlanc, Pharm.D. Clinical Pharmacist University Health | Shreveport Saturday, October 27, 2018 [email protected] 55

37 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

10:00—11:00 a.m. Hemostatic agents and their uses in coagulation disorders

R. Logan Murray, PharmD PGY1 Pharmacy Resident University Health Shreveport

0179-0000-18-036-L01-P/0179-0000-18-036-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: Technicians: 1. Recall the specific coagulation factor 1. Recall the brand and generic names of deficiencies in hemophilia A, hemophilia B commonly used hemostatic products. and von Willebrand disease. 2. Identify special storage and preparation 2. Summarize the goals of therapy for the requirements for commonly used treatment and von Willebrand disease. hemostatic products. 3. Assist in the selection of and appropriate hemostatic agent for the treatment of hemophilia A, hemophilia B and von Willebrand disease. 4. Determine if the dosing and administration of hemostatic agents are appropriate.

Dr. Murray has disclosed that she has no relevant financial relationships.

38 2

. Recall the specific coagulation factor deficiencies in hemophilia A, hemophilia B, and von Willebrand disease Hemostatic Agents & Their . Summarize the goals of therapy for the treatment of Uses in Coagulation Objectives hemophilia and von Willebrand disease Disorders for . Assist in the selection of an appropriate hemostatic agent for treatment of hemophilia A, hemophilia B, and von R. Logan Murray, Pharm.D. Pharmacists Willebrand disease PGY1 Pharmacy Resident University Health Shreveport . Determine if dosing and administration of hemostatic agents are appropriate

3 4

. World Federation of Hemophilia Guidelines . Guidelines for the Management of Hemophilia . Recall the brand and generic names of . National Hemophilia Foundation commonly used hemostatic products Objectives . MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Other . Identify special storage and preparation for Bleeding Disorders requirements for commonly used hemostatic products Technicians . National Heart, Lung and Blood Institute . The Diagnosis, Evaluation and Management of von Willebrand Disease

5 6

Hemophilia

Hemophilia A

• Classic hemophilia Hemophilia • Caused by a deficiency of factor VIII (FVIII) or antihemophilic factor (AHF) • Accounts for 80 to 85% of cases

Hemophilia B

• Christmas disease • Caused by deficiency of factor IX (FIX) • Accounts for 15‐20% of cases

Fast Facts. National Hemophilia Foundation. Accessed at https://www.hemophilia.org/About‐Us/Fast‐Facts, August 31 2018.

39 7 8

Hemophilia Severity

Severe Moderate Mild Hemophilia Treatment • Factor activity < 0.01 • Factor activity 0.01‐ • Factor activity > 0.05‐ units/mL (1%) 0.05 units/mL (1‐5%) 0.4 units/mL (5‐40%) • Spontaneous • Prolonged bleeding •Few symptoms; bleeding of the joints after minor trauma Excessive bleeding or surgery only with significant trauma or surgery

9 10

. To prevent and treat acute bleeding by Active • Goal is Bleeding hemostasis Hemophilia replacing the deficient clotting factor Treatment Treatment . To prevent recurrent joint bleeding Approach Primary & •Prevent Goals complications joint disease . IV factor replacement therapy for Secondary before it . Muscle contractures the treatment or prevention of Prophylaxis starts . Pseudotumor bleeding is the mainstay of • Aims to slow treatment for hemophilia . Severe arthropathy progression Tertiary of joint . Chronic pain and disability leading to orthopedic disease and Prophylaxis maintain surgery joint mobility

Srivastava A, Brewer AK, Mauser‐Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1‐47. Srivastava A, Brewer AK, Mauser‐Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1‐47.

11 12 Factor Replacement Therapy

Protocol Definition . Minimizes recurrent joint bleeding and Episodic (“On Demand”) Treatment Treatment given at the time of clinically evident bleeding Prophylactic damage that can lead to physical disability Continuous Prophylaxis Factor . Considered the standard of care in patients

Regular continuous treatment in the absence of documented joint disease; with severe hemophilia Primary prophylaxis Replacement Started before the second clinically evident large joint bleed and age 3 years Therapy . Goal: Maintain patient’s minimum factor level Regular continuous treatment started after 2 or more bleeds into large joints Secondary prophylaxis at ≥ 0.01 units/mL (1%) with regular infusions and before the onset of joint disease of factor products Tertiary prophylaxis Regular continuous treatment started after the onset of joint disease

Treatment given to prevent bleeding for periods not exceeding 45 Intermittent (“periodic”) prophylaxis weeks/year

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed Srivastava A, Brewer AK, Mauser‐Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1‐47. September 03, 2018.

40 13 14

. Produced with recombinant DNA technology . Derived from pooled plasma Recombinant Plasma- . Contamination of plasma pools with hepatitis B, hepatitis C, . Risk of transmitting infections through and HIV during the 1970s and 1980s resulted in virus Factor administration is low Derived transmission to patients with hemophilia Products . Generally favored over plasma‐derived Factor . Donor screening, testing of plasma pools for evidence of infection, viral reduction through purification steps, and viral products Products inactivation procedures have resulted in safer products

. Human or animal proteins are used in the . Viral inactivation procedures do not inactivate hepatitis A and production process of some recombinant outbreaks have been reported products and a theoretical risk of transmitting infection remains

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018. September 03, 2018.

15 16

• Both plasma‐derived and recombinant products can Anaphylaxis & induce immediate (type 1) hypersensitivity reactions Hypersensitivity • Immune reactions occur more with FIX than with FVIII Hemophilia A Reactions products Factor VIII Replacement • Approximately 3% of patients with hemophilia B experience anaphylactic reactions to FIX products Therapy • Higher purity products are less likely to cause allergic reactions

Carcao M, Moorehead P, Lillicrap D. Hemophilia A and B. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018.

17 18

Generations of 1st Generation Factor VIII • Appropriate dosing depends on: • Half‐life of infused factor • Contain human albumin as a stabilizing protein Recombinant Concentrate • Patient’s body weight Factor VIII 2nd Generation Replacement • Location and severity of bleed Products • Added sugar instead of albumin as a stabilizer, • Goal plasma levels but human albumin is still used in the culture process • Serious or life‐threatening bleeding requires peak factor levels of greater than 0.75 to 1 units/mL (75‐ 3rd Generation 100%) • Less severe bleeding may be treated with a goal of • Do not contain human protein either in the culture or stabilization process 0.3 to 0.5 units/mL (30‐50%) peak plasma levels

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018. September 03, 2018.

41 19 Suggested Plasma Peak Factor VIII Level 21 and Duration of Administration Desired Factor VIII Level to Site of Hemorrhage/Clinical Situation Duration • 2% rise in plasma level for every of unit FVIII infused per Maintain Factor VIII kilogram Joint 40 to 60 units/dL 1 to 2 days, may be longer if response is inadequate Superficial muscle/no neurovascular compromise 40 to 60 units/dL 2 to 3 days, sometimes longer if response is inadequate Concentrate • The following equation can be used to calculate an initial Initial: 80 to 100 units/dL Initial: 1 to 2 days Iliopsoas and deep muscle with neurovascular injury, or Maintenance: 3 to 5 days, sometimes longer as secondary dose: substantial blood loss Maintenance: 30 to 60 units/dL Replacement prophylaxis during physiotherapy • Initial: 80 to 100 units/dL Initial: 1 to 7 days CNS/Head Maintenance: 50 units/dL Maintenance: 8 to 21 days Initial: 80 to 100 units/dL Initial: 1 to 7 days Throat and neck • Half‐life of FVIII ranges from 8‐15 hours 0.5 Maintenance: 50 units/dL Maintenance: 8 to 14 days Initial: 80 to 100 units/dL Initial: 7 to 14 days Gastrointestinal • Generally necessary to administer 50% of the initial dose Maintenance: 50 units/dL Maintenance: Not specified Renal 50 units/dL 3 to 5 days about every 12 hours to sustain the desired level of FVIII Deep laceration 50 units/dL 5 to 7 days Preop: 80 to 100 units/dL Postop: 60 to 80 units/dL Postop: 1 to 3 days • Continuous infusion may be considered when prolonged Surgery (major) Postop: 40 to 60 units/dL Postop: 4 to 6 days treatment is required Postop: 30 to 50 units/dL Postop: 7 to 14 days Preop: 50 to 80 units/dL Surgery (minor) Postop: 30 to 80 units/dL Postop: 1 to 5 days depending on procedure type Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed Srivastava A, Brewer AK, Mauser‐Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1‐47. September 03, 2018.

21 22 Select Factor VIII Products Mix2Vial®

Brand Name Product Product Type Storage Preparation

Refrigerate for longest shelf‐life; 2nd Generation Recombinant Needleless reconstitution with Kogenate FS® May be kept at room temperature Factor VIII vial adapter for 12 months

Refrigerate for longest shelf‐life; 2nd Generation Recombinant Helixate FS® May be kept at room temperature Mix2Vial® Transfer System Factor VIII for 12 months

Refrigeration or room Hemofil M® Plasma‐Derived Factor VIII Double‐ended needle system temperature

Plasma‐Derived Factor VIII with Refrigeration or room Humate P® Mix2Vial® Transfer System Von Willebrand Factor temperature

National hemophilia Foundation NHF Medical and Scientific Advisory Council. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. April 2018. Accessed August 31, 2018. Package Inserts (see notes). Mix2Vial [Information]. Exton, PA: West Pharmaceutical Services, Inc.; 2017.

23 24 Needleless Reconstitution with Vial Adapter • Pharmacy is consulted to provide a preoperative FVIII Factor VIII dose. The patient is a 40 kg child with severe hemophilia Dosing A. The patient’s treatment team currently has plans for Twist Example minor surgery. Calculate an appropriate dose of FVIII. •

• Desired FVIII level prior to minor surgery is 50‐80 units/dL 0.5 Mix • Severe hemophilia patients have a baseline factor level of < 1% Attach

Rebinyn [package insert]. Plainsboro, PA: Novo Nordisk A/S; 2017.

42 25 26

• Recombinant FIX is considered the treatment Hemophilia B of choice for hemophilia B Hemophilia B Factor IX • Prothrombin complex concentrates (PCCs) that Factor IX Replacement Replacement contained other vitamin‐K dependent proteins Therapy Therapy (factors II, VII, and X) were used previously • Not recommended first‐line due to lower purity and thrombogenic potential

27 Suggested Plasma Peak Factor IX Level 29 and Duration of Administration

Site of Hemorrhage/Clinical Situation Desired Factor IX Level to Maintain Duration • 1% rise in plasma level for every of unit FIX infused per kilogram Factor IX Joint 40‐60 units/dL 1‐2 days, may be longer if response is inadequate • The following equation can be used to calculate an initial dose for Superficial muscle/no neurovascular compromise 40‐60 units/dL 2‐3 days, sometimes longer if response is inadequate Concentrate plasma‐derived products: Initial: 1‐2 days Iliopsoas and deep muscle with neurovascular Initial: 60‐80 units/dL Maintenance: 3‐5 days, sometimes longer as • injury, or substantial blood loss Maintenance: 30‐60 units/dL Replacement secondary prophylaxis during physiotherapy Initial: 60‐80 units/dL Initial: 1‐7 days CNS/head Maintenance: 30 units/dL Maintenance: 8‐21 days Initial: 60‐80 units/dL Initial: 1‐7 days • Due to lower recovery of recombinant products, dosing is Throat and neck Maintenance: 30 units/dL Maintenance: 8‐14 days Initial: 60‐80 units/dL Initial: 7‐14 days adjusted: Gastrointestinal Maintenance: 30 units/dL Maintenance: Not specified • Pediatric dosing: Renal 40 units/dL 3‐5 days Deep laceration 40 units/dL 5‐7 days Preop: 60‐80 units/dL • Adult dosing: Postop: Postop: 1.4 Surgery (major) 40‐60 units/dL 1‐3 days 30‐50 units/dL 4‐6 days 20‐40 units/dL 7‐14 days Preop: 50‐80 units/dL 1.2 Surgery (minor) Postop: 30‐80 units/dL Postop: 1‐5 days depending on procedure type Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018. Srivastava A, Brewer AK, Mauser‐Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1‐47.

29 30 Select Factor IX Products

Brand Name Product Product Type Storage Preparation Other • Pharmacy is consulted to provide an initial factor replacement Needleless Refrigeration or room Use within 3 hours of Factor IX dose for a patient with severe hemophilia B. The patient is a 60 BeneFix® Recombinant Factor IX reconstitution with vial temperature reconstitution adapter kg child and is currently suffering from intracranial hemorrhage. Dosing The physician has noted that he would like to use the brand Refrigerate for longest Recombinant Factor IX Needleless shelf‐life; May be kept at Use within 3 hours of name product BeneFix®. Calculate an appropriate initial FIX dose. ALPROLIX® with IgG‐1 Fc Domain reconstitution with vial Example room temperature for 6 reconstitution Fusion Protein adapter months • Recombinant product

Refrigerate for longest • Pediatric patient Needleless Pegylated shelf‐life; May be kept at Use within 4 hours of Rebinyn® reconstitution with vial • Recombinant Factor IX room temperature for 6 reconstitution adapter months Refrigerate for longest • Desired FIX level for management of hemorrhage of the CNS/head Plasma‐Derived Factor shelf‐life; May be kept at Mix2Vial® Transfer Use within 3 hours of 1.4 AlphaNine SD® IX room temperature for 1 System reconstitution is 60‐80 units/dL month • Severe hemophilia patients have a baseline factor level of < 1%

43 31 32

• Neutralizing antibodies to factors VIII and IX develop in Inhibitors in some patients Hemophilia • Development of an inhibitor is the most serious Treatment of Inhibitors complication of factor replacement therapy in Hemophilia • Risk of inhibitor development is highest in those with severe hemophilia A (FVIII deficiency) • Interferes with infused factor concentrate, rendering them ineffective

33 34 Products for Treatment of Hemophilia with Inhibitors • Low inhibitor titers • Higher doses of the specific factor (2‐3 times the usual Treatment of Brand Name Product Product Type Storage Preparation replacement dose) Hemophilia in • Increased dosing interval frequency

Patients with • High inhibitor titers Plasma‐Derived Activated BAXJECT II® Hi‐Flow Needleless FEIBA® Prothrombin Complex Room temperature • Impossible to administer enough FVIII or FIX to neutralize Transfer Device Concentrate (aPCC) Inhibitors the antibody and achieve a hemostatic plasma level • Treatment of bleeding episodes consists of agents that bypass the factor to which the antibody is directed • Prothrombin complex concentrates (PCCs) Traditional reconstitution Refrigeration or room product or Needleless • Activated prothrombin complex concentrates (aPCCs) – FEIBA® NovoSeven RT® Recombinant Factor VIIa temperature reconstitution product with vial • Recombinant factor VIIa (NovoSeven RT®) adapter • Emicizumab

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed National hemophilia Foundation NHF Medical and Scientific Advisory Council. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. April 2018. Accessed August 31, 2018. September 03, 2018. Package Inserts (see notes).

35 36

• Anamnestic response – Rapid antibody Adverse production upon subsequent exposure with Effects of the same antigen Bypassing • The aPCC contains trace FVIII and FIX Von Willebrand Disease Agents • May cause increase in inhibitor titers • In patients with newly diagnosed inhibitors, NovoSeven RT® should be used • Black box warning • Serious risk of thrombotic complications

44 37 38

. Caused by deficient or defective von . vWF mediates platelet adhesion to injured Von Willebrand factor Von blood vessel sites and promotes platelet Willebrand . Most common congenital bleeding disorder in Willebrand aggregation Disease the US Factor . Binds FVIII and protects it from degradation, . Occurs in men and women equally, but prolonging its half‐life women are more likely to experience . A deficiency of vWF reduces the half‐life and complications plasma level of factor VIII

Fast Facts. National Hemophilia Foundation. Accessed at https://www.hemophilia.org/About‐Us/Fast‐Facts, August 31, 2018. Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018.

39 40

Classification . Clinical manifestations are variable and some Clinical patients are asymptomatic Type 1 Type 2 Type 3 Presentation . Mucocutaneous bleeding • Most common type • Diagnosed in 20‐30% • Accounts for 1‐3% of . Easy bruising (70‐80% of cases) of affected patients cases . Postoperative bleeding • Mild to moderate • Bleeding •vWF nearly reduction in level of manifestations more undetectable and vWF with a similar severe than with with FVIII levels are very reduction in FVIII type 1 disease low • Bleeding symptoms • Severe clinical are mild to moderate phenotype

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018. McGraw‐Hill; Accessed September 03, 2018.

41 42

. The specific type of vWD, the location, and Von severity of bleeding determine the approach to Von Willebrand Disease Willebrand treatment Disease . Systemic treatment is used for uncontrolled Treatment bleeding and for prevention of bleeding with Treatment surgery Approach & . The goal of systemic therapy is to correct platelet adhesion and coagulation defects by either Goals stimulating the release of endogenous vWF or by administering products that contain vWF and factor VIII

45 43 44

. Replacement therapy with plasma‐derived . Stimulates the endothelial cell release of vWF Treatment vWF‐containing products is the treatment of Desmopressin and FVIII Approach choice for patients with types 2 and 3 vWD . Temporarily effective for patients with vWD . Patients with type 1 vWD unresponsive to who have adequate endogenous stores of desmopressin are also candidates for factor functional vWF replacement therapy . Dosed at 0.3 mcg/kg IV over 15‐30 minutes, . Recombinant factor VIII products contain no every 12 to 24 hours vWF and are inadequate for treatment of . Effect diminishes with repeat doses vWD

Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw‐Hill; Accessed September 03, 2018. McGraw‐Hill; Accessed September 03, 2018.

45 46 Plasma-Derived Factor VIII/vWF Complex Concentrates Condition Therapy Brand Name Specific Activity Storage Other Replacement (IU vWF/mg total protein) Major surgery Maintain factor VIII level ≥ 50% for 1 week

Therapy in Prolonged treatment in type 3 patients (> 7 days) Alphanate® 9‐28 Refrigeration or room temperature Use within 3 hours of reconstitution vWD Minor surgery Maintain factor VIII level ≥ 50% for 1‐3 days

Maintain factor VIII level > 20%‐30% for an Humate‐P® 3.6‐11.2 Refrigeration or room temperature Use within 3 hours of reconstitution additional 4‐7 days

Dental extraction Single infusion to achieve factor VIII level > 50%

Refrigerate for longest shelf‐life; Not indicated for treatment of Desmopressin prior to procedure for type I Wilate® >60 May be kept at room temperature hemophilia A; Use immediately after for 6 months reconstitution Spontaneous or Usually single infusion of 20‐40 units/kg posttraumatic bleeding

National hemophilia Foundation NHF Medical and Scientific Advisory Council. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. April 2018. Accessed August 31, 2018. Trinkman H, Beam D, Hagemann T. Coagulation Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: Package Inserts (see notes). McGraw‐Hill; Accessed September 03, 2018.

47 48

. Hemophilia and vWD are chronic conditions often The requiring complex, costly, and personalized therapies . Factor products for the treatment of acute bleeding Conclusion & Pharmacist’s episodes and prophylaxis are typically dispensed in hospital and specialty pharmacies Role . Patients should receive routine immunizations, including Assessment hepatitis A and B vaccines . Pharmacists should specifically be able to answer questions regarding treatment options, dosing, storage, and stability . Pharmacists also have a role in educating patients about product usage and recognizing signs and symptoms bleeding

46 50 51

The first‐line therapeutic approach to treating an active bleed in a patient with severe hemophilia Which is a true statement regarding prophylaxis without inhibitors is: therapy for hemophilia? A. Plasma derived factor replacement A. Not recommended by any national organization B. Recombinant factor replacement Question B. Recommended approach but optimal dosing Question and schedule is not well defined C. Activated prothrombin complex concentrates #1 #2 (aPCCs) C. Proven cost effective D. Desmopressin D. Patient compliance is not a factor in overall outcome E. Anti‐thrombolytic

52 53

Which of the following agents should be used to treat an acute bleed in a patient with hemophilia B Which of the following factor products can be with inhibitors? used to treat severe bleeding episodes in patients A. High doses of recombinant FVIII Question with von Willebrand disease? Question B. Low doses of recombinant FIX administered for A. Activated prothrombin complex concentrates long periods of time #3 B. Activated FVII #4 C. Activated prothrombin complex concentrates C. Recombinant FVIII D. Activated FVII D. Plasma derived FVIII

The appropriate approach to treating an acute bleed in a patient with hemophilia A with a 7BU inhibitor level is: Question Hemostatic Agents & Their Uses A. Activated prothrombin complex concentrates in Coagulation Disorders B. High dose recombinant FVIII #5 R. Logan Murray, Pharm.D. C. High dose plasma derived FVIII PGY1 Pharmacy Resident D. High dose recombinant FIX University Health Shreveport

47 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

1:00—2:00 pm Pharmacy Legislative and Administrative Update

Jeffery D. Evans, Pharm.D. Associate Professor of Pharmacy Practice College of Pharmacy, University of Louisiana at Monroe Clinical Assistant Professor of Family Medicine and Comprehensive Care College of Medicine, Louisiana State University Health Science Center - Shreveport

0179-0000-18-033-L03-P/0179-0000-18-033-L03-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: Technicians: 1. Outline potential applications of Board rule 1. Outline potential applications of Board rule changes to current pharmacy practice. changes to current pharmacy practice. 2. Identify areas of positive change in 2. Identify areas of positive change in upcoming rule and law changes. upcoming rule and law changes. 3. Recognize implications of recent opioid 3. Recognize implications of recent opioid abuse/misuse actions on pharmacy abuse/misuse actions on pharmacy practice and patient care. practice and patient care.

Dr. Evans has disclosed that he has no relevant financial relationships.

48 Objectives

At the end of the presentation the student: Legislative Update Should be able to discuss different bills that are in front of the State Legislature

Should be able to discuss different rule changes in the Louisiana Board of Jeffery D. Evans, Pharm.D. Pharmacy Director and Associate Professor School of Clinical Sciences

HB 45 - Requires third-party logistics providers to HB 150 - Authorizes the La BOP to waive license obtain controlled dangerous substance licenses and certification renewal fees for military spouses

HB - 45 Rep Connick HB 150 by Representative H. Bernard LeBas

‘Third-Party Logistics provider means a person who provides or coordinates Would add active duty military spouses (either pharmacist or pharmacy warehousing, facilitation of delivery, or other logistic services for a legend drug or technician) to the list of people the board may waive license/renewal fees legend device in interstate and intrastate commerce on behalf of the manufacturer, distributor, or dispense of a legend drug or legend device but does Effective Date 08/01/18 – Act 63 not take ownership of the legend drug or legend device nor have the responsibility to direct the sale or disposition of the legend drug or legend device.’

Would create a $50 annual license for TPLs

08/01/18 Effective Date Act 186

HB 151 - Revises the definition of ‘approved college HB 326 - Makes technical corrections to various provisions of law within the of pharmacy’ as used in the LPPA purview of the legislative committees on health and welfare

HB 151 - Representative LeBas HB - 326 by Rep Bob Hensgens

Deletes the requirement for foreign graduates to graduate from a College listed in the World Directory of Schools of Pharmacy Several word changes such as healthcare is now health care Allows board to create its own ‘educational equivalency’ mechanism

Act 64 – Effective Date 08/01/18 03/20 Passed House (91 - 1)

05/09 Passed Senate (32 – 0)

Act 206 – Eff 08/01/2018

49 HB 336 - Provides for a single preferred drug list in HB 384 - Creates and provides a state prescription Medicaid managed care. drug importation program HB 336 - Rep Kenny Cox HB 384 enter by Rep Talbot

Imports from Canada at the direction of the LDH with the BOP and Department of Insurance Changes the wording from ‘suggest’ to requires a single preferred drug list for the patients in Medicaid Managed Care. Requires an approved wholesaler to import the medications, then sell them to ONLY Louisiana licensed pharmacies 03/28 Passed (11 - 0) out of committee Drugs may not be dispensed/shipped out of State Was never voted on in the House Bans pharmaceutical manufacturers from being angry

04/05 Heard in Committee

HB 492 - Requires that pharmacists report to certain HB 547 Prohibits penalties for disclosure by parties when refills of certain psychiatric medications pharmacists of certain prescription drug cost go undispensed information HB 492 entered by Rep Bagley HB 547 entered by Rep LeBas

Would require that pharmacists notify the prescriber AND any person listed in the Would prohibit ‘gag’ orders of pharmacist with regards to drug costs records as a family member or designated contact Would make that portion of the contract unenforceable The BOP is to create a list and decide how long undispensed means Would have to offer to charge the patient the least cost

Heard in committee on 04/17/18 In committee and heard on 04/11/18

HB548 - Requires that the prescribers transmit HB 579 - Provides relative to the authorization for prescriptions for opioids to pharmacies electronically therapeutic use of marijuana

HB 548 by Rep Miller Entered by Representative James

Requires all prescribers (not veterinarians) to use electronic prescriptions by Adds severe muscle spasms, glaucoma, intractable pain and PTSD to list of 01/01/2020 approved uses

If there are fees per prescription, the pharmacy will pay them Adds vaporization to list of delivery mechanisms, not smoking. Smoking is bad.

Allows transfer of electronically prescribed controlled substances Passed committee 04/05

04/12 Passed the House (60 - 40) 05/16 Passed Senate (54 – 34) Passed committee on 04/04 (7-4) Act 708 eff 08/01/18 Died in the house

50 HB 627 Authorizes the recommendation of medical HB 748 - Establishes the Occupational Licensing marijuana for treating certain health conditions of Review Act persons with autism Entered by Rep Emerson Entered by Rep Lyons Begins with ‘ the right of an individual to pursue a lawful Adds certain forms of Autism to the approved list of conditions allowed to be occupation is a fundamental right.’ treated with marijuana Seeks to limit restrictions on who can do what. Boards should Children would need to see a pediatric specialist. Adults, not so much only regulate to protect consumers from significant harm

Act 496 – Eff August 2018 with research reporting due 2020 However ….. Was reduced to a bill that would require the Governor’s office to ensure Boards were needed.

SB 29 - Provides relative to a single uniform SB 90 - Provides relative to a voluntary nonopioid prescription drug prior authorization form directive form

Entered by Senator Mills Entered by Sen Mills

Would require ALL insurers to accept a State approved PA form Requires the Louisiana Department of Health to create and post a voluntary nonopioid form on the the website of the department

If a provider ignores the request in good faith, they can not be punished

Act 423 – Eff 01/01/19 (this is when the Boards must have an answer) Passed Senate (37 -0 )

04/27 Passed House (84 - 0)

Act 28 – Eff 08/01/18

SB 477 - Provides for electronic prescribing of noncontrolled legend drugs

SB 477 entered by Sn Lafleur

Really deals with Chart Orders So inpatient or LTCF only Board of Pharmacy Actions Allows for electronic prescribing, does not require it

Act 602 – Eff 08/01/18 – See Rule Changes

51 2018- A Update to immunizations 2018 - B Update to returning drugs

Requires pharmacists to update links within 24 hours Would allow pharmacies to take back medications to destroy them

If mass immunization event 72 hours They must be separated from other stock

Adequate supplies needed for management of anaphylactic reactions This applies to controls also (updates chapters 15, 25, 27)

Heard on 10/18/18 Heard on 10/18/18

2018 - C Investigation Drugs 2018 - D Notification of the departed

Updates Chapter 25 on Investigational drugs with CLEAR guidance on what to do Would require PICs to notify the BOP of any departed, licensed people

Updates Chapter 15 to allow hospitals to serve non-patients Would require owner of pharmacy to report EVERY licensed person no later than Dec 31st of each year

Approved by Reg committee 09/13/18 To be heard on 10/18/18

To be heard on 11/14/18 by full Board

2018 - E Naloxone tracking 2018 - F PBM Licensure

Updates PMP to require tracking of naloxone as a drug of concern Adds verbage to Chapter 24 for Pharmacy Benefit Managers Permits

For public health purposes Promulgated by the Board (you got an email)

Approved by the board, going out for promulgation

52 2018 - G Telepharmacy 2018 - H Penal updates

Changes the miles requirements from 20 to 10 miles Sadly the end of Penal, and will now be correctional center

Allows pharmacies in hospitals to be exempt from the miles requirement Pursuant to 2016 law, allows for returns to locally managed (parish) correction centers Allows pharmacies to petition the board for exemption from miles requirement

Adds lines that if pharmacy does more than 200 rxs per day they have to convert REMS drugs are excluded from returns to a community pharmacy line Heard on 10/18/18 To be heard 10/18/18

2018 -J PMP retention 2018 - K Veterinary hospitals

Clarifies the board to retain PMP data for 5 years Adds to Chapter 15 the veterinary hospital

Requires the board to ‘respond’ to requests for data In a teaching hospital

Owned or operated by a PUBLIC university TO be heard by full Board on 11/14/18 In Louisiana

To be heard by the Board on 11/14/18

2018 - L Refill dispensing 2018 - M Standards for Immunizations

Prohibits the dispensing of refills without a patient request Allows for offsite administration of immunizations

Requires access to emergency management medications to be present

Deleted and added to 2018 - A Remember dispensing is finalized when you give it to a patient….

To be heard by Board on 11/14/2018

53 2018 – N Standards for making copies of 2018 – P Prior Authorization Forms commercially available products ● Creates both the form a requirement to use it

● Copies must be different ○ Pushes enforcement off to Departments of Health and Insurance

○ Clinical differences must be justified BY PRESCRIBER ● Oddly appears in chapter 11 ■ 10% dosage changes not reasonable ● Drug shortages must appear on the FDA maintained list ● Has been sent for promulgation

To be heard 10/18/18

2018 – Q Eliminating the testing delay 2018 – R Pharmacy Technicians reciprocity

● Removes the waiting period of 1 year after the third failure of an exam ● Removes the work requirement in LA from Technicians from other states

○ For both Pharmacist and Pharmacy Technicians. ○ Requires they have at least 1 year of experience elsewhere

● To be heard by the Board on 11/14/18 To be heard by the Board on 11/14/18

2018 – S Removal of CE Requirements in main 2018 – T Access to PMP by epidemiologist office ● They get access ● Per Act 232 ● Would eliminate the requirement of paper copies of CE ● Was heard on 10/18/18

○ Allows for use of CPE Monitor as official record

○ You may be asked for a paper copy of the CPE Monitor

54 2018 – U Partial Filling of CIIs 2018 – V CDS licensure of TPLs

● Updates the rules to match the law ● No draft is ready yet

○ Allows for partial filling of any CII within 30 days of being written ● Heard on 10/18/18 ● Was heard on 10/18/18

2018 – U Rule making procedure update Federal Updates

● Required by ACT 454 Provider Status

● All request for rule changes must appear on Just as popular as ever

○ White paper Trying to now be lumped with opioid issues

○ 8 ½ x 11 inch Sen Kennedy

○ Margins of at least 1 inch Opioid Quota Reform Act

○ Not less than 10 characters per inch Sen Cassidy ○ Double Spaced, quotations though may be single spaced Know the lowest price Act

Protection from Overprescribing Act

Questions

55 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

2:00—3:00 p.m. Current trends and topics in diabetes management

Jamie Terrell, PharmD Clinical Pharmacist Morris and Dickson Employee Wellness Clinic, Shreveport, Louisiana Clinical Associate Professor, Department of Clinical Sciences University of Louisiana Monroe College of Pharmacy Shreveport, Louisiana

0179-0000-18-038-L01-P 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: 1. Identify patients at risk for T2DM and means of prevention. 2. Compare and contrast current diagnostic criteria for pre-DM and T2DM. 3. List current therapeutic goals for patients with T2DM. 4. Recognize and discuss recent changes to 2018 ADA Standards of Care.

Dr. Terrell has disclosed that he has no relevant financial relationships.

56 Disclosures

Current Trends and Jamie M. Terrell, Pharm.D. reports that she has no financial relationship with Topics in Diabetes any commercial supporters or Management providers.

JAMIE M. TERRELL, PHARM.D.

Objectives

1 2 3 4

Identify Compare and List current Recognize and patients at risk contrast current therapeutic discuss recent for T2DM and diagnostic goals for changes to 2018 means of criteria for pre- patients with ADA Standards prevention DM and T2DM T2DM of Care

https://www.cdc.gov/diabetes/library/socialMedia/infographics.html

https://www.cdc.gov/diabetes/library/socialMedia/infographics.html https://www.cdc.gov/diabetes/library/socialMedia/infographics.html

57 https://www.cdc.gov/diabetes/library/socialMedia/infographics.html https://www.cdc.gov/diabetes/statistics/slides/maps_diabetes_trends.pdf

Risk Factors for T2DM Ben Jones First- degree relative 55 year old attorney Insulin High-risk resistance 72”; 225 lbs; BMI = 30.5 race PMH: HTN (HCTZ 12.5mg daily) FHx: Physical Overweight or History Inactivity obese plus… of CVD Mom- HTN, T2DM, HLP, obesity Dad- deceased at age 45 (work accident) Brother- healthy; Sister- HTN; T2DM dx 2 weeks ago PCOS HTN Bikes for 1.5 hrs TIW (weather permitting) Lipids

American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2018; 41 (Suppl.1): S13-S27.

1 0

7 Standards of medical care in diabetes- 2018. American Diabetes Association. Diabetes Care. 2018;41(supp 1).

58 A1C 5.7- 2h plasma glucose 6.4% FPG > 126 mg/dL* >200 mg/dL during 2h plasma an OGTT* FPG 100- glucose 140- 125 mg/dL 199 mg/dL Diabetes during an Classic OGTT hyperglycemia A1C >6.5%* symptoms + random plasma glucose >200 Prediabetes mg/dL

* In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.

American Diabetes Association Standards of Medical Care in Diabetes. American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2018; 41 (Suppl.1): S13-S27. Classification and diagnosis of diabetes. Diabetes Care 2018; 41 (Suppl.1): S13-S27.

Ben sees his physician today and has After diagnosis… the following fasting labs drawn: Immunizations Referrals CMP- WNL except glucose 105 mg/dL  Annual influenza  Dilated eye exam A1c- 7.2%  Pneumococcal- 23 vs  Family planning 13 specialist Lipids- Total Chol- 185 mg/dL  Hepatitis B series  Registered dietician HDL- 65 mg/dL (ages 19-59)  DSMES  Shingles*  Dentist Trigs- 97 mg/dL  Mental health LDL = 101 mg/dL professional

American Diabetes Association Standards of Medical Care in Diabetes. Comprehensive Medical Evaluation and Assessment of Comorbidities. Diabetes Care 2018; 41 (Suppl.1): S28-S37.

Physical Activity

 >150min moderate-to-vigorous intensity aerobic activity per week Spread over at least 3 days NMT 2 days of inactivity  2-3 sessions/week of resistance exercises Nonconsecutive days  Decrease daily sedentary behavior  BIW-TIW: Flexibility and balance training for older adults

American Diabetes Association Standards of Medical Care in Diabetes. https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf Lifestyle Management. Diabetes Care 2018; 41 (Suppl.1): S38-S50.

59 Aspirin Therapy- low dose (81mg) BP management

Primary prevention: Goal: BP between <140/90 140/90 and BP >160/100 >50 years plus >1 risk factor: 160/100 FHx of premature ASCVD, HTN, smoking, HLP, albuminuria Albuminuria No Albuminuria No Albuminuria Albuminuria <50 years= not recommended Intermediate risk = clinical judgement ACEI, ARB, ACEI or ARB AND Choose 2 of 3: st ACEI or ARB CCB, or ACEI, ARB, CCB, Pregnant pts: end of 1 trimester to ↓ risk of thiazide CCB or thiazide or thiazide preeclampsia

American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular Disease and Risk Management. Diabetes Care 2018; 41 (Suppl.1): S86-S104. American Diabetes Association Standards of Medical Care in Diabetes. Management of Diabetes in Pregnancy. Diabetes Care 2018; 41 (Suppl.1): S137-S143. Cardiovascular Disease and Risk Management. Diabetes Care 2018; 41 (Suppl.1): S86-S104.

Ben’s sister- Bridget: 58 years old Lipid Management

<40 years + 40-75 years >75 years Any age ASCVD risk without without with Bridget has HTN and has been on: factors ASCVD ASCVD ASCVD HCTZ 25 mg daily

Consider Lisinopril 40 mg daily Moderate Moderate High moderate intensity intensity intensity intensity Amlodipine 10 mg daily statin statin statin statin Compliant with lifestyle modifications

Her BP today was 148/96. LDL still >70? Consider ezetimibe or PSCK9 American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular Disease and Risk Management. Diabetes Care 2018; 41 (Suppl.1): S86-S104. inhibitor

Statin intensity chart Lipid Management

Atorvastatin 40-80mg; Rosuvastatin 20-40mg

Atorvastatin 10-20mg; Rosuvastatin 5-10mg; Simvastatin 20- 40mg; Pravastatin 40-80mg; Lovastatin 40mg; Fluvastatin XL 80mg; Pitavastatin 2-4mg

Simvastatin 10mg; Pravastatin 10-20mg; Lovastatin 20mg; Pitavastatin 1mg

American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular Disease and Risk Management. Diabetes Care 2018; 41 (Suppl.1): S86-S104. AACE/ACE Consensus Statement. Endocrin Pract. 2018;24(1):91-100

60 Glycemic Targets

A1C Twice yearly if controlled (Q3m if therapy change or if not meeting targets) Goal: <7% for most nonpregnant patients Preprandial glucose: 80-130 Peak postprandial glucose: <180

American Diabetes Association Standards of Medical Care in Diabetes. American Diabetes Association Standards of Medical Care in Diabetes. Glycemic Targets. Diabetes Care 2018; 41 (Suppl.1): S55-S64. Glycemic Targets. Diabetes Care 2018; 41 (Suppl.1): S55-S64.

Hypoglycemia

Alert Clinically Severe- value- significant- Level 3 Level 1 Level 2

<70 mg/dL <54 mg/dL No specific threshold Treat with fast- Serious, Severe cognitive acting carbs and impairment Treatment options for Ben clinically requiring external possible important adjustment of assistance for glucose-lowering hypoglycemia recovery therapy American Diabetes Association Standards of Medical Care in Diabetes. Glycemic Targets. Diabetes Care 2018; 41 (Suppl.1): S55-S64.

Metformin Safe, effective, cheap*, may reduce CV events and death Beneficial effects on A1C, weight, and CV mortality B12 deficiency possible OK if CrCl >30mL/min GI upset, diarrhea, LA CI: CHF, CrCl <30mL/min, etc.

American Diabetes Association Standards of Medical Care in Diabetes. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care 2018; 41 (Suppl.1): S73-S85.

61 Current recs for T2DM Metformin

ASCVD No ASCVD

GLP-1 RA: SGLT2-I: SU, TZDs, GLP-1RA, liraglutide, empagliflozin, SGLT2-I, DPP4-I, semaglutide canagliflozin Basal insulin

American Diabetes Association Standards of Medical Care in Diabetes. American Diabetes Association Standards of Medical Care in Diabetes. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care 2018; 41 (Suppl.1): S73-S85. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care 2018; 41 (Suppl.1): S73-S85.

Cardiovascular Disease- Clinical Trials Cardiovascular Disease- Clinical Trials

Drug class Drug Impact on CVD Study GLP-1 Agonists Exenatide Ongoing trial EXSCEL Liraglutide* ↓ risk of CV death LEADER Drug class Drug Impact on CVD Study and total death Dulaglutide Ongoing trial REWIND SGLT2 inhibitors Canagliflozin ↓ risk of CV death CANVAS Albiglutide No ↑ CV risk HARMONY program meta- Dapagliflozin Ongoing Trial DECLARE-TIMI analysis Lixisenatide No ↑ CV risk ELIXA Empagliflozin* ↓ risk of CV death EMPA-REG Semaglutide ↓ risk of non-fatal SUSTAIN stroke and non- *Has FDA Indication fatal MI *Has FDA Indication

LEADER Cardiovascular Disease- Clinical Trials Liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) study. N Engl J Med 2016; 375: 311-322. Key Element Notes Drug class Drug Impact on CVD Study Patients Patients with T2DM with ASCVD or multiple risk factors DPP-4 Sitagliptin No ↑ CV risk TECOS inhibitors No ↑ HF hospitalization (n=9340) Intervention Liraglutide + other antihyperglycemics Saxagliptin No ↑ CV risk SAVOR-TIMI ↑ HF hospitalizations Comparator Placebo + other antihyperglycemics Alogliptin No inc. CV risk EXAMINE Outcomes Time-to-event first CV event- superior (13.0% vs 14.9%; Linagliptin Ongoing trials CAROLINA HR=0.89) CARMELINA Death from CV causes- superior (4.7% vs 6.0%; HR=0.78) All cause mortality- superior (8.2% vs 9.6%; HR=0.85) GI side effects more common but not pancreatitis

62 EMPA-REG CANVAS Empagliflozin regulatory outcome (EMPA-REG) study. N Engl J Canagliflozin and cardiovascular and renal events in type 2 Med 2015; 373: 2117-28. diabetes. N Engl J Med 2017; 377: 644-57.

Key Element Notes Key Element Notes Patients Patients with T2DM and ASCVD or multiple risk factors Patients Patients with T2DM with ASCVD or multiple risk factors (n=7020) (n=10,142) Intervention Empagliflozin 10mg or 25mg daily + other Intervention Canagliflozin 100mf or 300mg daily + other antihyperglycemics antihyperglycemics Comparator Placebo + other antihyperglycemics Comparator Placebo + other antihyperglycemics Outcomes Pooled analysis (both treatment doses of empagliflozin) Outcomes Fatal/Non-fatal stroke or MI– superior (26.9 vs 31.5*; HR=0.86) Composite endpoint- superior (10.5% vs 12.1%; HR=0.86%) All cause mortality– no difference (17.3 vs 19.5*; HR=0.87) CV death (3.7% vs 5.9%); HF (2.7% vs 4.1%); all cause Hospitalization for HF- superior (5.5 vs. 8.7*; HR=0.67) mortality (5.7% vs 8.3%) all superior. Amputation (6.3 vs 3.4*), fractures (15.4 vs 11.9*), GU GU infections more frequent infections in men *Event rate per 1000 patient-years

Summary

 Current therapies for patients with Current Trends and diabetes are expanding rapidly.  ASCVD risk is a key player in how we Topics in Diabetes determine what drug to provide patients.  Knowing goals for therapy and applying Management guideline-based care can help JAMIE M. TERRELL, PHARM.D. pharmacists help their patients.

63 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

2:00—3:00 p.m. Are you ready? Disaster Preparedness and Response for the Pharmacy Team

Jennifer Smith, PharmD, BCPS Gratis Clinical Instructor of Medicine LSU Health Sciences Center Shreveport Shreveport, LA Associate Professor University of Louisiana at Monroe School of Pharmacy Shreveport, LA Staff Pharmacist, PRN University Health Shreveport, LA

0179-0000-18-040-L04-P/0179-0000-18-040-L04-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: Technicians: 1. Recognize core competencies for disaster 1. Recognize core competencies for disaster medicine and public health. medicine and public health. 2. Describe key roles for pharmacists on a 2. Describe key roles for pharmacists on a disaster response team. disaster response team. 3. Choose useful resources to include in a 3. Choose useful resources to include in a disaster plan for training and education for disaster plan for training and education for healthcare providers in disaster response. healthcare providers in disaster response. 4. Propose an emergency response plan 4. Propose an emergency response plan highlighting pharmacist activities given a highlighting pharmacy technician activities disaster/emergency scenario. given a disaster/emergency scenario.

Dr. Smith has disclosed that he has no relevant financial relationships.

64 ARE YOU READY? DISASTER PREPAREDNESS AND RESPONSE FOR THE PHARMACY TEAM

Jennifer G Smith, PharmD, BCPS Associate Professor ULM College of Pharmacy, Shreveport Campus

OBJECTIVES: PHARMACISTS

¡ Recognize core competencies for disaster medicine and public health ¡ Describe key roles for pharmacists on a disaster response team ¡ Choose useful resources to include in a disaster plan for training and education for healthcare providers in disaster response ¡ Propose an emergency response plan highlighting pharmacist activities given a disaster/emergency scenario

OBJECTIVES: PHARMACY TECHNICIANS

¡ Recognize core competencies for disaster medicine and public health ¡ Describe key roles for pharmacy technicians on a disaster response team ¡ Choose useful resources to include in a disaster plan for training and education for healthcare providers in disaster response ¡ Propose an emergency response plan highlighting pharmacy technician activities given a disaster/emergency scenario

65 IT COULD HAPPEN…

¡ You are nearing the end of an overnight shift in the hospital when massive flash flooding occurs and your daytime relief pharmacists are unavailable by phone. Wi-fi networks have gone down so cell phone service is intermittent and streets are flooded so you don’t expect that anyone is going to make it in to work for the daytime shift. The weather forecast is for continued rain throughout the day. What are you going to do? ¡ Hurricane Florence – you live in western North Carolina and are safe from the flooding, but work at a partner hospital to the major health system providing service to the coastal areas that have been inundated with water, could you help provide relief for pharmacy services in the flooded areas in an emergency? How would you set it up? Who would be in charge?

CORE COMPETENCIES FOR DISASTER MEDICINE AND PUBLIC HEALTH

Highly specialized

Discipline/Profession specific

Role/Function/ Category specific

Core

Adapted from: Walsh L, et al. Disaster Med Public Health Preparedness. 2012;6:44-52.

CORE COMPETENCIES

¡ Article provides a list of 11 core competencies and 36 subcompetencies that are specific and measurable ¡ Complete list provided at end of presentation ¡ General competencies that can be adapted based on your profession and role

Walsh L, et al. Disaster Med Public Health Preparedness. 2012;6:44-52.

66 ASHP STATEMENT ON ROLE OF HEALTH-SYSTEM PHARMACISTS IN EMERGENCY PREPAREDNESS

“Every hospital and health-system pharmacist should ¡ Become well informed about the local history of and potential for natural disasters and industrial accidents, as well as the threat of terrorist attacks with WMD, including potential agents that could be used and the related diagnostic and treatment issues; ¡ Become thoroughly informed of local and institutional plans for emergency preparedness, especially those related to the distribution, control, and use of pharmaceuticals; ¡ Share with professional colleagues and patients evidence-based information on pharmaceuticals used to respond to disasters; ¡ Act assertively to prevent and allay panic and irrational responses to disasters; ¡ Strongly discourage individuals from developing personal stockpiles of pharmaceuticals for use in the event of chemical, biological, or nuclear terrorism; ¡ Consider volunteering in advance of a disaster to assist in (a) distributing emergency supplies of pharmaceuticals, (b) dispensing and administering medications and immunizations, and (c) managing the drug therapy of individual victims; and ¡ Develop and maintain first-aid skills and complete and maintain basic cardiac life support (BCLS) certification. BCLS certification may be required for administering injectable medications, such as vaccines.” ASHP. Am J Health-Syst Pharm. 2003; 60: 1993-5.

CORE COMPETENCIES

Apply your knowledge!

¡ Please review the table of competencies and subcompetencies provided. ¡ Which tasks stand out to you as a potential key activities or roles for pharmacists, pharmacy technicians or pharmacy students in a disaster or crisis situation?

KEY ROLES-WHO IS IN CHARGE?

¡ Disasters often occur with little or no warning and cause chaos and confusion ¡ Clearly defined roles help reduce chaos and avoid duplication of efforts ¡ At the state level, the governor is responsible for safety and welfare of people of that state or territory ¡ Usually delegates duties ¡ May request federal assistance ¡ At the parish level, the mayor is responsible for safety and welfare of people of their jurisdiction ¡ Usually delegate duties, often to an emergency preparedness ¡ May request state and, in some cases. federal assistance

67 KEY ROLES-WHO IS IN CHARGE?

¡ Caddo Parish Sheriff’s Office of Homeland Security and Emergency Preparedness ¡ Leads and supports efforts to prepare to, respond to, and recover from disasters ¡ Maintains and continuously updates the Emergency Operations Plan (EOP) as required by state law ¡ Includes responsibilities for government entities and (eg, law enforcement, fire/EMS, hospitals/medical systems, etc) ¡ Hospital/health system ¡ Hospital administration is responsible for activating emergency operations/services as needed

¡ Roles/procedures should be defined in hospital’s in-house emergency response plan

KEY ROLES – WHAT ABOUT ME?

¡ Pharmacists

¡ Pharmacy technicians

KEY ROLES – WHAT ABOUT ME?

¡ Pharmacists ¡ Supplies! Can help anticipate needed surge supplies based on type of disaster ¡ Drug information, especially if unusual biological/chemical exposure ¡ Alternative treatment options if usual treatment is out of stock/unavailable

¡ Pharmacy technicians ¡ Procurement of supplies and assist with substitutions if desired products are unavailable ¡ Assist with supply management/stocking based on what is commonly used in specialty units

68 ARE YOU READY?

¡ In a single state survey, hospitals were asked about their knowledge and ability to provide services in a mass casualty scenario. ¡ 17 sites (94.4%) reported having an institutional disaster preparedness protocol ¡ 10 (55.5%) had a specific plan for the pharmacy department ¡ 10 (55.5%) were unsure whether their hospital had an adequate supply of supplies commonly utilized in a mass casualty scenario ¡ Survey was limited by a low response rate (30%) ¡ Does your hospital have a institutional disaster preparedness protocol?

Awad NI, Cocchio C. P&T. 2015 Apr; 40(4): 264-267.

WHAT DO I NEED?

¡ Please form a group with 5-7 people sitting near you. A scenario will be provided for discussion.

Source: www.usatoday.com

SELECTED RESOURCES

¡ Ready.gov – Part of national public service campaign to provide education and resources for all Americans to “prepare for, respond to and mitigate emergencies, including natural and man-made disasters” ¡ Spanish language version available at Listo.gov ¡ NABP – Emergency and disaster preparedness and response planning: A guide for boards of pharmacy: https://nabp.pharmacy/wp-content/uploads/2016/07/06Emergency_Preparedness_Guide.pdf ¡ US DHH Public Health Emergency Page for Responders, Clinicians and Practitioners: https://www.phe.gov/Preparedness/responders/pages/default.aspx ¡ CDC Office of Public Health Preparedness and Response: https://www.cdc.gov/phpr/index.htm ¡ For the hospital: Joint Commission, AHRQ ¡ FEMA

69 ACTIVITY TIME!

¡ You have just discovered that your pharmacy/place of employment currently does NOT have an emergency response plan ! ¡ Please work with your neighbors to develop a list of priorities/outline to draft an emergency response plan. ¡ What are your priorities as a hospital pharmacist and/or pharmacy department administrator? ¡ Consider difference in needs/plans for an acute disaster event (natural disaster or terrorist attack) vs recovery/post-disaster management (ongoing needs after an acute disaster) ¡ What other stakeholders (outside pharmacy) should you consult during development of the plan? ¡ Focus on a few items that you, as a pharmacist or pharmacy technician, could specifically do to contribute in an emergency response situation at your pharmacy/place of employment.

SUMMARY

¡ Consider your own skills, abilities, and experience when developing a disaster plan ¡ Know who to call and where to find information about the disaster plan for your place of employment ¡ Seek out training based on your interests and keep certifications updated

REFERENCES

¡ American Society of Health-System Pharmacists. ASHP statement on the role of health-system pharmacists in emergency preparedness. Am J Health-Syst Pharm. 2003; 60:1993-5. ¡ Alkhalili M, Ma J, Grenier S. Defining roles for pharmacy personnel in disaster response and emergency preparedness. Disaster medicine and public health preparedness. 2017; 11(4): 496-504. ¡ Awad NI, Cocchio C. Assessment of hospital pharmacy preparedness for mass casualty events. P&T. 2015 Apr; 40(4): 264-267. ¡ D’Arrigo T. Disaster Strikes! Are you ready to help your community? Pharmacy Today. 2017: 23(8);34 -37. ¡ Menighan TE. Pharmacists have major role in emergency response. Pharmacy Today. 2016; 22(8): 8. ¡ Pincock LL, Montello MJ, Tarosky MJ, Pierce WF, Edwards CW. Pharmacist readiness roles for emergency preparedness. Am J Health-Syst Pharm. 2011; 68:620-623. ¡ Walsh L, Subbarao I, Gebbie K, et al. Core competencies for disaster medicine and public health. Disaster Med Public Health Preparedness. 2012; 6:44-52.

70 Core Competencies and Subcompetencies for Disaster Medicine and Public Health From: Walsh L, Subbarao I, Gebbie K, et al. Core competencies for disaster medicine and public health. Disaster Med Public Health Preparedness. 2012; 6:44-52.

Core Competency Subcompetency 1.0 Demonstrate personal and family preparedness 1.1 Prepare a personal/family disaster plan for disasters and public health emergencies 1.2 Gather disaster supplies/equipment consistent with personal/family plan 1.3 Practice one’s personal/family disaster plan annually 1.4 Describe methods for enhancing personal resilience, including physical and mental health and well- being, as part of disaster preparation and planning 2.0 Demonstrate knowledge of one’s expected 2.1 Explain one’s role within the incident management hierarchy and chain of command established within role(s) in organizational and community response one’s organization/agency in a disaster or public health emergency plans activated during a disaster or public health 2.2 Prepare a personal professional disaster plan consistent with one’s overall agency, organizational, emergency and/or jurisdictional plan 2.3 Explain mechanisms for reporting actual and potential health threats through the chain of command/authority established in a disaster or public health emergency 2.4 Practice one’s personal professional disaster plan in regular exercises and drills 3.0 Demonstrate situational awareness of 3.1 Identify general indicators and epidemiological clues that may signal the onset or exacerbation of a actual/potential health hazards before, during, and disaster or public health emergency after a disaster or public health emergency 3.2 Describe measures to maintain situational awareness before, during, and after a disaster or public health emergency 71 4.0 Communicate effectively with others in a 4.1 Identify authoritative sources for information in a disaster or public health emergency disaster or public health emergency 4.2 Explain principles of crisis and emergency risk communication to meet the needs of all ages and populations in a disaster or public health emergency 4.3 Identify strategies for appropriate sharing of information in a disaster or public health emergency 4.4 Identify cultural issues and challenges in the development and dissemination of risk communication in a disaster or public health emergency 5.0 Demonstrate knowledge of personal safety 5.1 Explain general health, safety, and security risks associated with disasters and public health measures that can be implemented in a disaster or emergencies public health emergency 5.2 Describe risk reduction measures that can be implemented to mitigate or prevent hazardous exposures in a disaster or public health emergency 6.0 Demonstrate knowledge of surge capacity 6.1 Describe the potential impact of a mass casualty incident on access to and availability of clinical and assets, consistent with one’s role in organizational, public health resources in a disaster or public health emergency agency, and/or community response plans 6.2 Identify existing surge capacity assets which could be deployed in a disaster or public health emergency 7.0 Demonstrate knowledge of principles and 7.1 Discuss common physical and mental health consequences for all ages and populations affected by a practices for the clinical management of all ages disaster or public health emergency and populations affected by disasters and public 7.2 Explain the role of triage as a basis for prioritizing or rationing health care services for all ages and health emergencies, in accordance with populations affected by a disaster or public health emergency professional scope of practice 7.3 Discuss basic lifesaving and support principles and procedures that can be utilized at a disaster scene 8.0 Demonstrate knowledge of public health 8.1 Discuss public health consequences frequently seen in disasters and public health emergencies principles and practices for the management of all 8.2 Identify all ages and populations with functional and access needs who may be more vulnerable to ages and populations affected by disasters and adverse health effects in a disaster or public health emergency public health emergencies 8.3 Identify strategies to address functional and access needs to mitigate adverse health effects of disasters and public health emergencies 8.4 Describe common public health interventions to protect the health of all ages and populations affected by a disaster or public health emergency 9.0 Demonstrate knowledge of ethical principles to 9.1 Discuss ethical issues likely to be encountered in disasters and public health emergencies protect the health and safety of all ages, 9.2 Describe ethical issues and challenges associated with crisis standards of care in a disaster or public populations, and communities affected by a health emergency disaster or public health emergency 9.3 Describe ethical issues and challenges associated with allocation of scarce resources implemented in a disaster or public health emergency 10.0 Demonstrate knowledge of legal principles to 10.1 Describe legal and regulatory issues likely to be encountered in disasters and public health protect the health and safety of all ages, emergencies populations, and communities affected by a 10.2 Describe legal issues and challenges associated with crisis standards of care in a disaster or public disaster or public health emergency health emergency 10.3 Describe legal issues and challenges associated with allocation of scarce resources implemented in a disaster or public health emergency 10.4 Describe legal statutes related to health care delivery that may be activated or modified under a state or federal declaration of disaster or public health emergency

72 11.0 Demonstrate knowledge of short- and long- 11.1 Describe clinical considerations for the recovery of all ages and populations affected by a disaster or term considerations for recovery of all ages, public health emergency populations, and communities affected by a 11.2 Discuss public health considerations for the recovery of all ages and populations affected by a disaster or public health emergency disaster or public health emergency 11.3 Identify strategies for increasing the resilience of individuals and communities affected by a disaster or public health emergency 11.4 Discuss the importance of monitoring the mental and physical health impacts of disasters and public health emergencies on responders and their families Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting

3:00—4:00 p.m. "Put it in Reverse!": Strategies for Reversal of Anticoagulants

Molli Gremillion, PharmD PGY1 Pharmacy Resident LSU Ochsner Shreveport Shreveport, LA

0179-0000-18-031-L01-P/0179-0000-18-031-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity

Objectives:

Pharmacists: Technicians: 1. Compare and contrast the mechanisms of 1. Identify commonly used anticoagulants action and bleeding risks of current 2. Identify commonly used anticoagulant available anticoagulants. reversal agents. 2. Identify and describe therapeutics agents 3. Describe storage and stability parameters used in the reversal of anticoagulants. for individual anticoagulant reversal 3. Select an appropriate reversal agent for agents. each specific anticoagulant and calculate an appropriate dose on patient-specific parameters. 4. Develop a plan for monitoring and management of patients at high risk of bleeding associated with anticoagulants.

Dr. Gremillion has disclosed that she has no relevant financial relationships.

73 Disclosure

“Put it in reverse!” • I have no relevant conflicts of interest or financial disclosures in Strategies for reversal of anticoagulants relation to this continuing education presentation

Molli Gremillion, PharmD PGY-1 Resident University Health Shreveport

Pharmacist Objectives Pharmacy Technician Objectives

• Compare and contrast the mechanisms of action and bleeding risks • Identify commonly used anticoagulants of current available anticoagulants • Identify commonly used anticoagulant reversal agents • Identify and describe therapeutic agents used in the reversal of anticoagulants • Describe storage and stability parameters for individual anticoagulant reversal agents • Select an appropriate reversal agent for each specific anticoagulant and calculate an appropriate dose based on patient specific parameters • Develop a plan for monitoring and management of patients at high risk of bleeding associated with anticoagulants

3 4

Clotting Cascade Anticoagulants and Bleeding Risk

Blockage of coagulation factors

• Institute for Safe Medication Practices (ISMP) list of high Decreased thrombin alert medications production  Last published August 2018

• All increase risk of bleeding Decreased conversion of fibrinogen to fibrin

Decreased formation https://www.emsworld.com of stable clot

http://www.nature.com/articles/nrdp20156/figures/2 Eikelboom J. Am J Med. 2016 August. 5 6

74 Anticoagulant Pharmacokinetics Anticoagulant Monitoring

Anticoagulant effects on coagulation assays Drug Half-life (hours) Primary elimination (%) Anti Xa Anticoagulant aPTT PT/INR TT ECT Heparin 1 to 2.5 Renal levels LMWH 4.5 to 7 Renal (40%) Heparin ↑ -- ↑↑-- Warfarin 20 to 60 Renal (92%) LMWH ↑ or -- -- ↑↑-- Dabigatran 12 to 17 Renal (80%) Warfarin ↑↑ ↑-- -- Rivaroxaban 5 to 9 Renal (66%) / Hepatic (28%) Apixaban 8 to 15 Hepatic (63%) FXa inhibitors ↑ or -- ↑ or -- ↑ -- -- Direct thrombin Edoxaban 10 to 14 Renal (50%) ↑↑ or -- -- ↑↑ inhibitors

Frontera J. Neurocrit care. 2016 December. Funk D. Blood. 2012 December 7 Siegal D. Blood. 2014 February 8

Bleeding risk Resources for Anticoagulant Reversal

DOAC bleeding risk compared to warfarin Major bleeding Drug Trial % per year CHEST NCCS/SCCM ACC (DOAC v warfarin) (2012) (2016) (2017) Dabigatran RE-LY 3.11 v 3.36 (p 0.31) Rivaroxaban ROCKET AF 3.6 v 3.4 (p 0.58) Apixaban ARISTOTLE 2.13 v 3.09 (p<0.001) Edoxaban ENGAGE AF TIMI 48 2.75 v 3.43 (p<0.001) *Main group studied in all trials were patients with atrial fibrillation

Frontera J. Neurocrit care. 2016 December. Holbrook A. CHEST. 2012 February. Tomaselli G. J Am Coll Cardiol. 2017 February. Eikelboom J. Am J Med. 2016 August. 9 10

Indications for Anticoagulant Reversal Overview of Reversal Agents

• Major Bleed  Decrease in Hgb > 2 g/dL Prothrombin Protamine Vitamin K Fresh frozen  Administration of > 2 units of PRBCs complex plasma  Bleed at anatomically critical site (ex: brain, GI tract) sulfate (phytonadione) concentrates  Hemodynamic instability  SBP <90 mmHg or ↓ in SBP > 40 mmHg

• Emergency surgery Idarucizumab Andexanet alfa Ciraparantag

Tomaselli G. J Am Coll Cardiol. 2017 February. 11 12

75 Protamine sulfate Protamine sulfate

Heparin reversal • Forms stable salt with heparin causing inactivation of both drugs • 1 mg protamine: 100 units heparin • May repeat dose with 0.5 mg protamine: 100 units heparin if aPTT • Reverses heparin and low molecular weight heparin (LMWH) remains elevated • Do not use in patients with fish allergy or other protamine • Only last 2 to 2.5 hours due to short half-life containing medications (ex: NPH) • aPTT monitoring • 10mg/mL vial AWP= $25 • 5 to 15 minutes after initial dose, then 2 to 8 hours post dose

Burnett A. BMJ 2017 May. Protamine [prescribing information]. 2016 December. 13 Frontera J. Neurocrit care. 2016 December. 14

Protamine Dosage Calculator Protamine sulfate

LMWH reversal • 1mg protamine: 1mg enoxaparin (last injection < 8 hours)

• 0.5mg protamine: 1mg enoxaparin (last injection > 8 hours)

• Re-dose with 0.5mg protamine: 1mg enoxaparin if bleeding > 4 hours after first dose

Burnett A. BMJ. 2017 May. Frontera J. Neurocrit care. 2016 December. 15 Clincalc.com/Protamine 16

Protamine sulfate Assessment Question #1

Administration • What lab parameter should be monitored after administering •Max dose: 50 mg protamine? •Max rate: 5 mg/min (severe hypotension and anaphylactoid-type reaction) (A) INR •IV push or IVPB over 10 minutes •Dilute with NS or D5W (B) PT (C) ECT Storage (D) aPTT

• Storage: room temperature between 15 and 30o C • Supplied • 10mg/ml (5mL and 25mL vials)

Protamine [prescribing information]. 2016 December. 17 18

76 Assessment Question #1 Vitamin K (phytonadione)

• What lab parameter should be monitored after administering • No Vitamin K recommended protamine? INR 4.5 to 10 (A) INR (B) PT • 2.5 to 5 mg oral Vitamin K once (C) ECT INR>10 (D) aPTT • 5 to 10mg IV Vitamin K PLUS Major bleeding 4F-PCCs

19 Holbrook A. CHEST. 2012 February. 20

Vitamin K (phytonadione) Vitamin K (phytonadione)

Administration • Fatal hypersensitivity reactions with IV administration • Avoid IM due to hematoma formation • Pearls • May be diluted in NS, D5W, or D5NS  High dose vitamin K may lead to warfarin resistance for up to 1 week • Maximum rate: 1mg/min  More rapid and predictable reduction in INR with IV vs oral/SC Storage  Delayed correction of coagulopathy due to INR lag time • Protect from light  Do not use IV formulation in neonates: contains benzyl alcohol • Supplied as: • 1mg/0.5mL injection vials • AWP (5 vials)=$1,080 • 5mg tablets • AWP (1 tablet)=$66.99

Phytonadione injection [package insert]. 2004 November. 21 Phytonadione injection[package insert]. 2004 November. 22

Prothrombin Complex Concentrate 4F-PCC (Kcentra)

Three Factor PCC •Factor II (3F-PCC) •Factor IX AWP (70 kg)= $4,165 •Factor X Warfarin Reversal

Inactivated Four Factor •Factor II INR >2.0 to < 4.0 >4.0 to < 6.0 > 6.0 or Major bleed PCC •Factor IX Dose 25 units/kg 35 units/kg 50 units/kg (Kcentra/4F-PCC) •Factor X Max dose 2500 units 3500 units 5000 units AWP (70kg)=$9,695 • Factor VII (inactivated) • Recommended first line by CHEST, NCCS/SCCM and ACC Activated Four Factor PCC •Factor II • Must be given with 10 mg IV Vitamin K •Factor IX (FEIBA/aPCC) •Factor X AWP (70 kg)= $15,190 • Factor VII (activated)

FEIBA (anti-inhibitor coagulant complex) [prescribing information]. 2018 April. Kcentra (prothrombin complex concentrate human) [prescribing information]. 2017 August. Profilnine (factor IX complex) [prescribing information]. 2017 March. 23 Kcentra (prothrombin complex concentrate human) [prescribing information]. 2017 August. 24

77 4F-PCC Dosage Calculator 4F-PCC (Kcentra)

DOAC Reversal Class DTIs FXa inhibitors 1st dose 50 units/kg 50 units/kg • Only for warfarin dosing 2nd dose May give an extra 25 units/kg if clinically necessary • Kcentra.com/dosage- calculator or iPhone app Max dose 5000 units

• Recommended as first line by CHEST, NCCS/SCCM and ACC • Doses only used in setting of acute ICH • Use only if ICH within 3 to 5 half lives or decreased renal function

25 Heidbuchel H. Europace. 2015 October. 26

4F-PCC (Kcentra) 4F-PCC (Kcentra)

Administration

• Always at room temperature • Rate: 0.12 mL/kg/min (max rate 8.4 mL/min) • Increased risk of thrombosis and anaphylaxis

Storage

• Refrigerate (15 to 25o C) • Do not freeze

Khorsand N. Haemotologica. 2012 April. Klein L. Ann Emerg Med. 2015 September. Majeed et al. Blood. 2017 October. Kcentra (prothrombin complex concentrate human) [prescribing information]. 2017 August. Shulman S. Thromb Haemostat. 2018 May. 27 28

4F-PCC (Kcentra) aPCC (FEIBA)

• Factor eight bypassing inhibitor activity (FEIBA)  Most commonly used in hemophilia A with inhibitors  Recommended by NCCS/SCCM and ACC as alternative to 4F-PCC • 4F-PCC v FFP  N= 212 • Max daily dose: 200 units/kg  103 4F-PCC v 109 FFP  Volume overload Drug class Dose  1% v 5% Vitamin K antagonists 25 to 100 units/kg  Infusion times 50 units/ kg if less than 3 to 5 half-lives of Oral anti-Xa  25 min v 2h liver failure Direct thrombin 50 units/kg if less than 3 to 5 half-lives or inhibitors renal failure

FEIBA (anti-inhibitor coagulant complex) [prescribing information]. 2018 April. Frontera J. Neurocrit care. 2016 December. Kcentra (prothrombin complex concentrate human) [prescribing information]. 2017 August. 29 Tomaselli G. J Am Coll Cardiol. 2017 February. 30

78 aPCC (FEIBA) Assessment Question #2

Administration

• Complete infusion within 3 hours • Which of the following is a risk when using FFP instead of 4FPCC? • Max rate: 2 units/kg/minute (A) Tachyphylaxis • Plastic luer lock syringe only (B) Volume overload • Increased risk of thrombosis (C) Antibody formation (D) Thrombosis Storage

• Room temperature (15 to 25o C) • Protect from light • Supplied as 500, 1000, and 2500 unit vials

FEIBA (anti-inhibitor coagulant complex) [prescribing information]. 2018 April. 31 32

Idarucizumab Assessment Question #2

• Binds free and thrombin bound dabigatran and • Which of the following is a risk when using FFP instead of 4FPCC? neutralizes it’s activity (A) Tachyphylaxis (B) Volume overload • Black box warning (C) Antibody formation  Thromboembolic and ischemic events (D) Thrombosis • AWP (5 g dose)=$4,200

https://newdrugapprovals.org/2016/04/26/idarucizumab/

33 Praxbind (idarucizumab) [prescribing information]. 2018 March. 34

REVERSE-AD trial (2015) Idarucizumab

Primary Administration Groups outcome • 5g dose: 2.5g/50mL x 2 doses 15 minutes apart Patients with •IV infusion or bolus Normal dTT 98% serious bleeding • Administer within one hour Normal ECT 89% (Group A) • Initiate dabigatran within 24h after end of infusion Idarucizumab 5g IV Storage Patients needing Normal dTT 93% emergent surgery • Stable for 6 hours after opening Normal ECT 88% (Group B) • Refrigerate unopened vials • Protect from light

Praxbind (idarucizumab) [prescribing information]. 2018 March. Pollack C. N Engl J Med. 2015 June. 35 36

79 Andexanet alfa ANDEXXA-A trial (2015)

• Inhibits direct and indirect factor Xa % decrease in inhibitors Interventions anti Xa activity (A v P) • Black box warning  Thromboembolic and ischemic Andexanet alfa 94 vs 21 events 400mg bolus P<0.001 • Supply limited until early 2019 (30mg/min) Apixaban 5mg BID • AWP (400 mg + 480 mg/120 min)= x 3 doses $59,400 Andexanet alfa 400mg bolus + 92 vs 33 • AWP (800 mg + 960 mg/120 min)= 4mg/min CI x 120 P<0.001 $121,000 mins

https://pbrainmd.wordpress.com/2015/12/20/reversal-of-factor-xa-inhibitors-the-2-annexa-trials/

Andexxa (andexanet alfa) [prescribing information]. 2018 May. 37 Siegal DM. N Engl J Med. 2015 November. 38

ANDEXXA-R trial (2015) Andexanet alfa

Factor Xa < 8 hours or Last dose > 8 hours % decrease in inhibitor unknown anti Xa activity Interventions (A v P) Rivaroxaban < 10 mg Low dose >10 mg or Low dose Rivaroxaban High dose Andexanet alfa unknown 92 v 33 800mg bolus P<0.001 (30mg/min) Rivaroxaban 20mg Apixaban < 5 mg Low dose QD x 3 doses > 5 mg or Low dose Andexanet alfa Apixaban High dose 800mg bolus + 97 v 45 unknown 8mg/min CI x 120 P<0.001 mins Low dose: 400 mg IV bolus (30mg/min) followed by 4mg/min infusion up to 120 min High dose: 800 mg IV bolus (30mg/min) followed by 8mg/min infusion up to 120 min

Siegal DM. N Engl J Med. 2015 November. 39 Andexxa (andexanet alfa) [prescribing information]. 2018 May. 40

Andexanet alfa Ciraparantag (PER 977)

Phase I (Edoxaban) • 60 mg edoxaban x 1 dose in 80 male subjects Administration • Ciraparantag 100 to 300mg given baseline • 0.22 micron filter required hemostasis restored in 10 to 30 minutes • Minimal stability data • Put into empty PVC or polyolefin IV bag after reconstitution Phase I (LMWH) • 1.5 mg/kg in 40 healthy volunteers Storage • Ciraprantag 100 to 300mg given reduction in WBCT to < 20 % • Vial: 8 hours (room temperature); 24 hours (refrigerator)

• IV bag:8 hours (room temperature);16 hours (refrigerator) • Works through non covalent hydrogen bonds and charge-charge interactions • Do not freeze • Currently in Phase II studies

Andexxa (andexanet alfa) [prescribing information]. 2018 May. 41 Ansell J. Thromb Res. 2016 July. 42 Burnett A. BMJ. 2017 May.

80 Cost Comparison Assessment Question #3

• 80 yo F (75 kg) presents to the ED with an acute ICH. She currently Reversal Agent Cost takes warfarin 5mg once daily for Afib. Her INR today is 4.8. What Protamine 50 mg IV $125 reversal agent and dose would you recommend to reverse her bleed? Vitamin K 5 mg tablet $66.99 Vitamin K 10 mg IV $1,080 4F-PCC (3,500 units for 70kg person) $9,695 Idarucizumab 5 g IV $4,200 Andexanet alfa (low dose) $59,400 Andexanet alfa (high dose) $121,000

43 44

Assessment Question #3 Key Points and Summary

• 80 yo F (75 kg) presents to the ED with an acute ICH. She currently takes warfarin 5mg once daily for Afib. Her INR today is 4.8. What Resources Indications Monitoring reversal agent and dose would you recommend to reverse her bleed?  4F-PCC PLUS Vitamin K CHEST aPTT  50 units/kg 4F-PCC for major bleed (max dose 5000 units) guidelines (2012) Major Bleeds  50 units x 75 kg= 3750 units 4F-PCCs (round to nearest vial size) PT/INR  Vitamin K 10mg IV/IM x 1 dose over 10 minutes NCCS/SCCM Anti Xa levels guidelines (2016) Emergency TT ACC expert surgery consensus (2017) ECT 45 46

Key Points and Summary “Put it in reverse!”

Protamine Andexanet Strategies for reversal of anticoagulants Vitamin K PCCs/FFP Idarucizumab sulfate alfa

Factor Xa Molli Gremillion, PharmD Heparin Warfarin Warfarin Dabigatran inhibitors PGY-1 Resident University Health Shreveport LMWH DOACs

81 Louisiana Society of Health-System Pharmacists 2018 Midyear Meeting NOTES

Thanks for attending the 2018 LSHP Midyear Meeting. We hope to see you next year!