The Kentucky Pharmacist- - November/December 2020 by Kentucky Pharmacists Association

Official Journal of the Kentucky Pharmacists Association

TABLE OF CONTENTS FEATURES

Mission Statement: To advocate and advance the pharmacy profession to improve the health of Kentuckians.

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Turning Tragedy into Giving Back |8|

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A Global Pandemic: Once a History Lesson Now a Modern-Day Reality – A Comparison Between the Spanish Flu and COVID-19 Pandemic |20|

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Telepharmacy Management – Opportunities and Challenges |32|

On the Cover COVID-19

Editorial Office: ©Copyright 2020 to the Kentucky Pharmacists Association. The Kentucky Pharmacist is the official journal of the Kentucky Pharmacists Association published bi-monthly. The Kentucky Pharmacist is distributed to KPhA members, paid through allocations of membership dues. All views expressed in articles are those of the writer, and not necessarily the official position of the Kentucky Pharmacists Association. Publisher: Sam Willett Managing Editor: Sarah Franklin Editorial, advertising and executive offices at 96 C Michael Davenport Blvd., Frankfort, KY 40601. Phone: 502.227.2303 Fax: 502.227.2258. Email: info@kphanet.org. Website: www.kphanet.org.

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IN EVERY ISSUE President’s Perspective |3| November CE Article |10| November Quiz |18| November CE Answer Sheet |19| December CE Article |25| December Quiz |30| December Answer Sheet |31| Pharmacy Law Update |36| Pharmacy Policy Issues |38| New KPhA Members |33|

ADVERTISERS APSC |7| PTCB |24| EPIC |39| CMP Pharma |Back Cover| Pharmacists Mutual |42| Cardinal |43| APMS |35|

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FEATURE Article Turning Tragedy into giving back Kentucky Pharmacists Association member Sarah M. Lawrence has worked to turn a personal tragedy into a commitment to serve the less fortunate in our community. In July 2008 Sarah lost her four-year-old daughter Riley Jane and her five-year-old niece Claudia Faye Wadlington to a hit and run driver, in an incident that shocked the Louisville community. Since that time, Sarah and her husband David, joined by sons Henry (born 2011) and Sam (born 2012) have worked to honor Riley and Claudia’s memory through acts of service and charity. One of their efforts is the Riley Jane Lawrence Scholarship at the Center for Gifted Studies, Western Kentucky University. This scholarship provides funds for a gifted and talented student of limited means to attend a summer enrichment program at WKU. Amanda Lich, Senior Philanthropy Officer for WKE shared the following about Sarah’s efforts: “As is often the case in philanthropy, Sarah’s fundraising and volunteer efforts have followed her passions. As a gifted young person, Sarah herself participated in the programming offered at The Center for Gifted Studies at WKU. When her daughter, Riley Jane, lost her life in a tragic accident, she took a personal tragedy and transformed it into a life-changing opportunity by creating the Riley Jane Lawrence Scholarship Fund for VAMPY (The Summer Program for Verbally and Mathematically Precocious Youth). She has held various fundraisers (virtually and in person) to solicit support for the fund and has actively engaged in stewarding every gift to the fund by conveying to donors her heartfelt appreciation. Sarah is a natural fundraiser and those around her are inspired to give in response to her personal commitment and her belief in the program benefiting from her efforts.” Outreach to those experiencing homelessness is another area of interest for the Lawrence family. Since 2017 they have been involved with an organization known as Snacks in Sacks, which provides bags of snack food for distribution to individuals living in camps and on the streets of Louisville. In December 2018, Sarah and David held their inaugural Kindness Party in honor of Riley’s birthday. In the weeks leading up to the party, they gathered donations from family and friends using an online wish list and met on Riley’s birthday with a group of about 25 friends to assemble the food into bags of non-perishable snacks. 400 bags were created at the first Kindness Party, and the event has been held three more times since, netting a remarkable 3464 bags for distribution by homeless outreach crews in the Louisville area. Rev. Darryl Glass from the Street Reach ministry had this to say about Sarah’s impact on his outreach: “Sarah’s work with the Snacks in Sacks organization with regards to our street outreach has been invaluable. There is no way that we could continue to serve every day without the snack bags she is responsible for providing. They are such a popular mainstay in the homeless community. I am so grateful for all she has done.” Recently, Sarah has taken a leadership role with Snacks in Sacks, organizing events (pre-COVID), managing the group’s online wish list, and building the organization’s web page. Since the start of the COVID-19 pandemic, although the organization has been unable to organize large snack bag filling events, Sarah has helped to keep its outreach alive, marshalling resources and keeping supporters engaged. In July 2020, the Lawrence family hosted a socially distanced snack bag filling event, collecting supplies from supporters all over the country and inviting other families to join them, one household at a time, in making snack bags outside, with masks and other safety precautions. Every night for a week, the Lawrence family along with friends and family worked to make snack bags with the donated supplies, and the result at the end of the week was an impressive 1283 snack bags. Trisha Drake, founder and President of |8| Kentucky Pharmacists Association | November/December 2020

Snacks in Sacks, said of Sarah’s leadership: “There has been a steady increase in community participation with Snacks in Sacks over the past couple of years and it is largely due to Sarah's leadership. She has a lot of fresh ideas and is generous with her time by responding promptly to email requests, planning large scale events, and organizing the donations we receive. Without Sarah, I would not be able to keep up with the growth of Snacks in Sacks. I am grateful for her influence and compassion.” A tragedy like the loss of a child is a life-altering event from which one may never fully recover. Sarah and David Lawrence, along with their children, have found a way to channel their pain into positive action for their community. For more information about their efforts, or to offer your support, please don’t hesitate to reach out to Sarah at sarahlawrencerx@gmail.com.

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NOVEMBER CPE Article Review of Direct Acting Oral Anticoagulants Authors: Kaylee Hall, PharmD Candidate 2022; Jordan Spurling, PharmD Candidate 2022; Mark Huffmyer, PharmD, BCGP, BCACP, CACP The authors declare that there are no financial relationships that could be perceived as real or apparent conflicts of interest. Universal Activity # 0143-0000-20-011-H01-P &T 2.5 Contact Hours Expires 12/14/23 Learning Objectives: At the conclusion of this Knowledge-based article, the reader should be able to: 1.

Understand the mechanism of actions, approved indications, side effects, reversal agents, drug-drug interactions and drug-food interactions of DOACs.

Evaluate the use of DOACs in special populations.

Evaluate peri-procedural management of DOACs.

4. Compare and contrast DOACs to warfarin

Introduction For decades, warfarin, a vitamin K antagonist, was the only oral anticoagulant available on the market in the United States. While effective at treating and preventing thromboembolic events, warfarin requires close monitoring due to its narrow therapeutic index, which is further complicated by its many drug-drug and drug-diet interactions. This makes it cumbersome and costly to manage [1]. In 2010, a new oral anticoagulant with a novel mechanism of action was approved and several drugs have followed since then. Direct acting oral anticoagulants (DOACs), include dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban, so called because of their direct mechanism of action. Warfarin exhibits its affect by depleting functional vitamin K reserves and therefore, reducing the synthesis of vitamin K dependent clotting factors [2]. DOACs, sometimes referred to as non-vitamin K dependent or novel oral anticoagulants (NOACs), act directly on specific clotting factors to produce their anticoagulant effect. Since the approval of the DOACs, there has been a declining use of warfarin each year while the use of DOACs continue to rise [3]. |10| Kentucky Pharmacists Association | November/December 2020

Compared to warfarin, DOACs require less monitoring, have less drug-drug interactions, drug-diet interactions, and can reduce the risk of hemorrhage [4]. These advantages have made DOACs the recommended treatment over warfarin for DVT/PE by the CHEST Guidelines [5] and recommended for stroke prevention in non-valvular atrial fibrillation by the American College of Cardiology [6]. In this article, we will discuss the mechanisms of action, side effects, drug-drug interactions, drug-diet interactions, reversal agents, periprocedural management and special populations of DOACs and, in addition, how they compare to warfarin. We will focus on the four most commonly prescribed DOACs, dabigatran, rivaroxaban, apixaban and edoxaban. These medications are often seen in the pharmacy and are considered to be high-risk medications by the Institute for Safe Medication Practices (ISMP) due to the risk of bleeding associated with them [7]. Understanding the DOACs, their properties and side effects can help to improve on patient care by expanding the knowledge of community pharmacists.

Understanding the DOACs

the prevention of major cardiovascular events in patients with CAD and PAD [9]. Rivaroxaban works Many factors are considered in choosing the most by the inhibition of factor-Xa, which inhibits the appropriate DOAC for each individual patient. conversion of prothrombin to thrombin. The maxiThese factors include indication, drug-drug interacmum effects of rivaroxaban can be seen within 2 tions, side-effects, kidney function, and other pahours of administration, with a half-life of 5-9 hours. tient specific factors. Like warfarin, the DOACs Rivaroxaban is 66% renally eliminated and 28% have a major side effect of bleeding and bruising, eliminated in the feces, causing increases in expothough in studies comparing warfarin to the DOsure in both renal and hepatic impairment. Doses ACs, the DOACs have been shown to have less of 15mg or greater should be taken with food to enbleeding risk [8]. In general, DOACs are eliminated sure adequate absorption. Tablets can be crushed both renally and hepatically to varying degrees. and administered in applesauce if there is difficulty DOACs are faster acting than warfarin and anticoswallowing. Rivaroxaban dosing is dependent on agulation effects are reversed quickly upon disconindication and renal function but is typically dosed tinuation. While frequent INR monitoring is needed once or twice daily. [11] for warfarin this is not true for the DOACs, though other parameters including kidney and liver function need to be monitored, albeit less frequently, Apixaban over the course of treatment. Warfarin also has Apixaban is FDA approved to reduce the risk of many more drug- drug and drug-food interactions stroke in patients with nonvalvular atrial fibrillation, compared to the DOACs. The DOACs interact with for prophylaxis of DVT/PE in patients after hip/knee medications that affect P-glycoprotein transporters replacement and DVT/PE treatment and recur(P-gp). Rivaroxaban and apixaban also have drug rence [9]. Apixaban, like rivaroxaban, is a factor-Xa interactions with CYP3A4 inhibitors/inducers. inhibitor and has a similar side effect profile. The maximum effect of apixaban can be seen within 34 hours of administration, with a half-life of 8-15 Dabigatran hours. Apixaban is excreted in both the urine (26%) Dabigatran is FDA approved to reduce the risk of and the feces; however, among the DOACs it is stroke in patients with nonvalvular atrial fibrillation, least reliant on the kidneys. It can be taken without for the treatment of DVT/PE after treatment with regards to meals and can be crushed and adminisparenteral anticoagulants for 5-10 days and, to retered in applesauce if there is difficulty swallowing. duce the risk of recurrence of DVT/PE [9]. Apixaban is typically dosed twice daily. [12] Dabigatran acts as a direct thrombin inhibitor, which inhibits the conversion of fibrinogen into fibrin. The maximum effects of dabigatran can be Edoxaban seen within 1-2 hours of administration, with a halfEdoxaban is FDA approved to reduce the risk of life of 12-17 hours. Dabigatran is the least reliant on stroke in patients with nonvalvular atrial fibrillation the liver compared to the other DOACs and is preand for treatment of DVT/PE after treatment with dominantly renally eliminated (80%), thus in paparenteral anticoagulation for 5-10 days [9]. Like tients with impaired renal function, half-life and dabigatran, edoxaban requires a heparin lead-in drug exposure increase. Aside from bleeding and prior to use for treatment for acute DVT/PE. Edoxabruising, common side effects include nausea, ban is a factor-Xa inhibitor similar to rivaroxaban heartburn and abdominal pain. Dabigatran should and apixaban. The maximum effects of edoxaban be administered with a full glass of water and can can be seen within 1-2 hours of administration, with be taken with meals to help reduce the incidence a half-life of 8-10 hours. Edoxaban is excreted about of heartburn. This capsule cannot be crushed or 50% in the urine. Edoxaban should not be used in opened because it may lead to an increase in adpatients with a CrCL >95ml/min, which may limit verse reactions. Dabigatran is typically dosed twice clinical utility. Edoxaban can be taken without redaily [10]. gard to meals and may be crushed and mixed into applesauce or water if there is difficulty swallowing. Edoxaban is typically dosed once daily. [13] Rivaroxaban Rivaroxaban is FDA approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation, Betrixaban for prophylaxis of DVT/PE in patients after hip/knee Betrixaban is the newest DOAC and was recently replacement, DVT/PE treatment and recurrence FDA approved in 2017 for VTE prophylaxis in acutely and, is the only DOAC currently FDA approved, for ill medical patients [14]. For the purpose of this arti|11| www.KPHANET.org

Table 1: DOACs Summary [2, 10, 11, 12, 13]

Approval year in the US Mechanism of Action

Time to peak therapeutic effect Half-life Renal elimination Drug interactions

Warfarin

Dabigatran

Rivaroxaban

Apixaban

Edoxaban

1954

2010

2011

2012

2015

Competitive inhibition of vitamin K epoxide reductase complex 1 (VKORC1) 5-7 days

Direct Thrombin Inhibitor

Direct Factor Xa Inhibitor

1-2 hours

2-4 hours

3-4 hours

1-2 hours

20-60 hours

12-17 hours

5-9 hours

8-15 hours

10-14 hours

Primarily hepatic metabolism Extensive

80%

33%

25%

35-39%

P-gp

P-gp, CYP3A4

P-gp

Table 2: DOAC Dosing

Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism)

Dabigatran

Rivaroxaban

CrCl

CrCl > 50 ml/min: 20 mg once daily with evening meal

30 ml/min: 150 mg BID

CrCl 15-30 ml/min: 75mg BID CrCl <15 ml/min: avoid use

CrCl 15-50 ml/min: 15 mg once daily with food CrCl <15: avoid use

Treatment of DVT and PE

CrCl > 30 ml/min: 150 mg BID after 510 of parenteral anticoagulation

15 mg BID with food for 21 days, then 20 mg daily with food

Reduction in the risk of recurrence of DVT and PE

CrCl > 30 ml/min: 150 mg BID after previous treatment

10mg daily without regard to meals, after 6 months of therapeutic anticoagulant treatment

VTE prophylaxis in total hip or knee arthroplasty

CrCl > 30 ml/min: 110 mg on the first day then 220 mg daily

10 mg once daily beginning 6 to 10 hours postoperatively or when hemostasis established.

Stable coronary artery disease or peripheral artery disease

CrCl ml/min: 2.5 mg BID with 81 mg Aspirin CrCl < 15ml/min: avoid use

Table 2 shows indications and recommend dosing of the DOACs according to the package inserts for each drug [10, 11, 12, 13]. |12| Kentucky Pharmacists Association | November/December 2020

cle, we will focus on dabigatran, rivaroxaban, apixaban and edoxaban.

Special Populations Chronic Kidney Disease and End Stage Renal Disease DOACs are largely renally eliminated and are therefore dose adjusted based on creatinine clearance (CrCl), with the exception of apixaban. Apixaban requires a dose decrease if two out of three of the following criteria are met: age years, body weight 60kg or serum creatinine 1.5mg/dL. [10, 11] In clinical efficacy and safety trials of apixaban, patients on dialysis and patients with a CrCl <15ml/min were not enrolled. However, pharmacokinetic data may suggest possible use in this patient population [12]. Retrospective studies have looked at the use of apixaban, at both 2.5mg BID and 5mg BID dosing, compared to warfarin in patients with end stage renal disease. The use of apixaban over warfarin in this patient population appears to be both safer and more effective, though a dose recommendation cannot be determined without further prospective trials [15].

months has to be reconsidered based on the patient and cancer status [18]. Apixaban and dabigatran are not currently recommended by guidelines to be used in cancer patients at this moment, though prospective randomized control trials are underway. Obesity In 2016, the International Society on Thrombosis and Haemostasis (ISTH) released guidelines on the use of DOACs in obese patients. Based on PK/PD data the ISTH does not recommend the use of DOACs in patients with a BMI >40 kg/m2or >120kg due to the risk of underdosing and limited efficacy data in this population [19].

In a retrospective study, comparing the recurrence of VTE in patients being treated with DOACs compared to warfarin showed no difference in the recurrence of VTE within 12 months [20]. Further retrospective studies investigating the use of DOACs in obese patients have been done that show evidence supporting the use of rivaroxaban and apixaban in obese patients. In obese patients, Rivaroxaban should be considered over apixaban [21] due to Rivaroxaban and dabigatran should be monitored closely in patients with CrCl<30ml/min and avoided the low volume of distribution, which would make it less affected by body weight [22]. Further proin patients with CrCl <15ml/min due to lack of data spective trials are needed to best assess which anti[11]. Edoxaban is unique when you consider that it coagulants and dosing are most appropriate in this cannot be used in patients with adequate renal function (CrCl >95ml/min), however there is no data patient population. suggesting use in patients with CrCl <15ml/min [13]. Though recommendations may be made in patients with CrCl of 15-30 ml/min, with careful monitoring and dose adjustments when appropriate, patients treated with DOACs with a CrCl <30 ml/min may have increased bleeding risk compared to those treated with warfarin [16]. Currently, warfarin remains the recommended oral anticoagulation agent in the population. Additional patient factors need to be considered when determining treatment options for this patient population. Cancer-associated VTE Prior to the approval of DOACs, low molecular weight heparin (LMWH) was recommended as the drug of choice for cancer associated VTE and still is by the most current 2016 CHEST guidelines [17]. The American Society of Clinical Oncology updated their guidelines in 2019 on the treatment of patients with cancer with an established VTE to prevent recurrence. Rivaroxaban is the only DOAC that is recommended for initial treatment and can be considered for long-term use up to 6 months. Edoxaban can be considered for long-term use after the initial use of LMWH. Use beyond 6

Hepatic Impairment All DOACs are metabolized to some extent by the liver. Patients with hepatic impairment should be evaluated using the Child-Pugh score. Dabigatran is the least metabolized by liver compared to the other DOACs. However, it is not recommended for patients with severe hepatic impairment but may be considered in patients with mild to moderate impairment [23]. Rivaroxaban should be avoided in patients with moderate to severe liver impairment. Apixaban is not recommended in patients with severe hepatic impairment but may be considered in patients with mild to moderate impairment. Edoxaban can be used in patients with mild hepatic impairment but is not recommended in patients with moderate to severe impairment [24]. Pregnancy The use of DOACs during pregnancy have not yet been studied and are not recommended to be used in woman who are pregnant or considering becoming pregnant. LMWH is the drug of choice in this patient population per CHEST guidelines. [25] |13| www.KPHANET.org

Bariatric Surgery Bariatric surgery, depending on the type of surgery performed, can significantly affect the absorption of medications. Patients who require anticoagulation therapy post-bariatric surgery are recommended to take warfarin due to the ability to monitor INR and dose adjust accordingly. DOACs are not recommended in this patient population until further studies are done [26]. Pediatrics

helps to identify cases where minimizing therapy cessation interval of anticoagulant is essential. Estimating risk for patients on anticoagulation depends on a variety of factors including patient indication and comorbidities, as well as the type of procedure being performed and estimated recovery time. In patients with atrial fibrillation, a CHADSVASC score is used to estimate the risk of stroke. For patients with a history of venous thromboembolism, risk is based on severity of previous thromboembolism events, how recently these events occurred, and the patient's hypercoagulable state. Patients with mechanical heart valves are assessed by collecting information about additional risk factors and assessing prosthesis. If risk factors are suddenly increased due to a recent embolism, surgery may need to be postponed based on a riskbenefit evaluation. If a patient has multiple risk factors, all should be taken into account. [29]

In pediatric patients, the anticoagulant most commonly used is heparins or vitamin K antagonists using weight-based dosing for most indications. All DOACs are currently undergoing or planning investigational studies to assess the benefits and risks while also configuring age-specific formulations [27]. To date all studies involving DOACs have been Next, it is important to determine the schedule of in patient populations over the age of 18. therapy interruption. The schedule is dependent on the specific agent being considered. Typically, warfarin will require a longer therapy interruption, apMechanical Heart Valve Patients proximately 5-7 days, while DOACs require a much At the time of this writing, the only oral anticoagu- shorter interruption of about 1-4 days. Providers lation option for patients with a mechanical heart must also consider the patient's renal and hepatic valve is warfarin. None of the DOACs are currently function to determine schedule effectively. The fiindicated in this patient population. One clinical nal step to consider is whether to use bridging antitrial published in 2012 evaluated dabigatran in this coagulation. In many cases, bridging anticoagulapopulation. It was halted early due to the tion is not necessary, due to an increased risk of dabigatran group having significantly more throm- bleeding without reduction of thromboembolism botic effects and an excess of major bleeding com- rate. Bridging anticoagulation with heparin or low pared to the warfarin group [28]. molecular weight heparin may be beneficial in some patients taking warfarin who have high thromboembolic risk. [30] Periprocedural Interruptions When considering therapy interruption of a DOAC For patients on anticoagulation therapy that unfor a procedure, guidelines suggest a comprehendergo surgery, the risk of thromboembolism is insive approach centered on communication becreased due to the interruption of that anticoagula- tween the provider managing the DOAC, the protion therapy for the sake of the procedure. It is im- vider performing the procedure, and the paportant in these cases to estimate thromboembolic tient/caregiver concerning the continued managerisk and bleeding risk, to determine the timing of ment of the therapy. If therapy interruption is unaanticoagulation interruption, and determine voidable, the provider is advised to consider the pawhether to use bridging anticoagulation therapy. tient's renal function and DOAC bleeding risk to The first step is to estimate a patientâ&#x20AC;&#x2122;s bleeding determine therapy interruption timeline as well as risk. A patientâ&#x20AC;&#x2122;s bleeding risk is primarily deterrestarting therapy timeline. The use of routine mined by the type and urgency of the surgery bebridging therapy is not recommended during thering performed, as well as patient specific factors apy interruption of DOACs. [31] such as patientâ&#x20AC;&#x2122;s age and history of bleeding. In Anticoagulation therapy interruption is not necesprocedures with low or no estimated bleeding, ansary for any procedures associated with minimal or ticoagulation therapy should not be interrupted. no bleeding risk. In low bleeding risk patients, the When determining a patient's bleeding risk, it is DOAC should be restarted approximately 24 hours important to keep in mind that higher bleeding post-operatively. If a patient is at high risk, DOAC risk requires higher need for perioperative hemoshould be postponed to 48-72 hours after procestasis and therefore a longer period of therapy indure or whenever hemostasis has been achieved. terruption. [29] [31] The next step of estimating thromboembolic risk |14| Kentucky Pharmacists Association | November/December 2020

Table 3: Perioperative DOAC Management

Table 3 represents the amount of time necessary to hold each DOAC perioperatively in accordance with the patientâ&#x20AC;&#x2122;s creatinine clearance. [32]

Reversal Agents While anticoagulation therapy is highly efficacious, complications such as bleeding are not uncommon. Estimates of the effect of anticoagulants find an approximately 2-fold increase in bleeding rates for patients on warfarin compared with patients only taking aspirin [33]. For this reason, use of accurate bleeding risk assessment tools incorporating individual risk factors are essential in clinical prescribing. Despite these assessment tools, it is possible for patients to experience a hemorrhage while taking an anticoagulant. For this reason, there are effective reversal agents to combat this adverse event [33]. In the event of a minor bleed, such as a nosebleed lasting less than 25 minutes, general supportive measures may be used such as discontinuation of the offending agent and investigational analysis of hemorrhage source. For major bleeding events, such as blood in the stool, more intensive management may be called for. Management of major bleeding includes prompt control of the hemorrhages by mechanical compression, surgical or endoscopic hemostasis, radiological interventional procedures, transfusion of blood components and hemodynamic support with fluid replacement as well as the use of adjunctive hemostatic agents (i.e., antifibrinolytics or desmopressin) [33].

experiencing either, administration of reversal agent is typically not warranted, and the bleed can be cared for routinely [34]. Warfarin is reversed most effectively by a vitamin K1 infusion administered. In less emergent situations, oral Vitamin K1 can be given in a tablet form when patient is nonbleeding and has an INR above 4.5 [35]. While Vitamin K1 is a quick and cost-effective reversal agent for warfarin, it will not reverse or have any effects on DOACs. There are two reversal agents approved by the FDA in the United States for DOAC-induced bleeding: Idarucizumab and Andexanet alfa. A third agent called ciraparantag, used for the reversal of rivaroxaban, apixaban, edoxaban, dabigatran and heparins, is currently awaiting phase 3 trials [36].

Indarucimab is effective for reversal of dabigatran induced bleeding and is effective within 4 hours of administration with 67.7% of patients stopped bleeding within 24 hours. Some patients may require an additional dose, so the pharmacist must ensure that prescribers have stopped all other antiplatelet drugs, NSAIDs, and anticoagulation agents. Andexanet alfa is approved for reversal of life-threatening bleeding for factor Xa inhibitors such as rivaroxaban and apixaban. The black box warning for Andexanet alfa includes arterial and venous thromboembolic events, ischemic events Use of a reversal agent is warranted when a patient (including myocardial infarction and ischemic has a life-threatening bleed or is undergoing an in- stroke), cardiac arrest, and sudden death. Due to vasive emergency procedure. If the patient is not these adverse effects, it is important to monitor pa|15| www.KPHANET.org

tients for thromboembolic effects and initiate anticoagulation therapy as soon as appropriate. Andexanet alfa is a biologic that will need reconstitut8. ing which will take time. Cost may also be a barrier to using Andexanet alfa. [37] Conclusion Prior to the 2010 approval of dabigatran, warfarin was the only available oral anticoagulant available in the United States. Since then, the DOACs have had an expanding role in clinical practice due to the ease of dosing, lack of monitoring and shorten half-life compared to warfarin. The use of these DOACs is still be investigated in many special populations, including obese patients, pediatrics and bariatrics, but may be a considerable option in the future. As the DOACs become more prevalent it is important to remember they are considered a highrisk medication and they require healthcare professionals to stay up to date on their uses in clinical, ambulatory and community settings. References 1.

Schulman, S., Anderson, D. R., Bungard, T. J., Jaeger, T., Kahn, S. R., Wells, P., & Wilson, S. J. (2010). Direct and indirect costs of management of long-term warfarin therapy in Canada. J Thromb Haemost, 8(10), 2192-2200. doi:10.1111/j.1538-7836.2010.03989.x

Warfarin. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view.

Barnes, G. D., Lucas, E., Alexander, G. C., & Goldberger, Z. D. (2015). National Trends in Ambulatory Oral Anticoagulant Use. Am J Med, 128(12), 1300-1305.e1302. doi:10.1016/j.amjmed.2015.05.044

/2018-08/highAlert2018-Acute-Final.pdf Accessed 11/05/2020 Zhou, Y., Ma, J., & Zhu, W. (2020). Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation Across BMI Categories: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs, 20(1), 51-60. doi:10.1007/s40256-019-003624 Bacchus, F., & Schulman, S. (2015). Clinical experience with the new oral anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol, 35(3), 513-519. doi:10.1161/atvbaha.114.303396

10. Dabigatran. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view. 11.

Rivaroxaban. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view.

12. Apixaban. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view. 13. Edoxaban. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view. 14. Betrixaban. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 5 Aug 2020; cited 14 Aug 2020]. Available from: http://online.lexi.com. Subscription required to view. 15. Hylek, E. M. (2018). Apixaban for End-Stage Kidney Disease. Circulation, 138(15), 1534-1536. doi:10.1161/circulationaha.118.036449

16. Weber, J., Olyaei, A., & Shatzel, J. (2019). The efficacy and safety of direct oral anticoagulants in patients Xian, Y., Xu, H., O'Brien, E. C., Shah, S., Thomas, L., Penwith chronic renal insufficiency: A review of the literacina, M. J., . . . Hernandez, A. F. (2019). Clinical Effecture. Eur J Haematol, 102(4), 312-318. tiveness of Direct Oral Anticoagulants vs Warfarin in doi:10.1111/ejh.13208 Older Patients With Atrial Fibrillation and Ischemic Stroke: Findings From the Patient-Centered Research 17. Kearon, C., Akl, E. A., Ornelas, J., Blaivas, A., Jimenez, D., Bounameaux, H., . . . Moores, L. (2016). AntithromInto Outcomes Stroke Patients Prefer and Effectivebotic Therapy for VTE Disease: CHEST Guideline and ness Research (PROSPER) Study. JAMA Neurol, 76(10), Expert Panel Report. Chest, 149(2), 315-352. 1192-1202. doi:10.1001/jamaneurol.2019.2099 doi:10.1016/j.chest.2015.11.026 Cesarman-Maus, G., & Ruiz-ArgĂźelles, G. J. (2017). News in the Indications of Direct Oral Anticoagulants 18. Key, N. S., Khorana, A. A., Kuderer, N. M., Bohlke, K., Lee, A. Y. Y., Arcelus, J. I., . . . Falanga, A. (2020). Venous According to the American College of Chest PhysiThromboembolism Prophylaxis and Treatment in cians 2016 Guidelines. Curr Drug Metab, 18(7), 651-656. Patients With Cancer: ASCO Clinical Practice Guidedoi:10.2174/1389200218666170413154226 line Update. J Clin Oncol, 38(5), 496-520. Hirsh, J., Fuster, V., Ansell, J., & Halperin, J. L. (2003). doi:10.1200/jco.19.01461 American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circu- 19. Martin, K., Beyer-Westendorf, J., Davidson, B. L., Huisman, M. V., Sandset, P. M., & Moll, S. (2016). Use of the lation, 107(12), 1692-1711. direct oral anticoagulants in obese patients: guiddoi:10.1161/01.Cir.0000063575.17904.4e ance from the SSC of the ISTH. J Thromb Haemost, Institute for Safe Medication Practice (2018) List of 14(6), 1308-1313. doi:10.1111/jth.13323 High-Alert Medications https://www.ismp.org/sites/default/files/attachments 20. Coons, J. C., Albert, L., Bejjani, A., & Iasella, C. J. (2020).

|16| Kentucky Pharmacists Association | November/December 2020

21.

22.

23.

24.

25.

Effectiveness and Safety of Direct Oral Anticoagulants lenges and emerging issues. J Thromb Haemost, 16(2), versus Warfarin in Obese Patients with Acute Venous 196-208. doi:10.1111/jth.13913 Thromboembolism. Pharmacotherapy, 40(3), 204-210. 31. Burnett, A. E., Mahan, C. E., Vazquez, S. R., Oertel, L. B., doi:10.1002/phar.2369 Garcia, D. A., & Ansell, J. (2016). Guidance for the pracCovert, K., & Branam, D. L. (2020). Direct-acting oral tical management of the direct oral anticoagulants anticoagulant use at extremes of body weight: Litera(DOACs) in VTE treatment. J Thromb Thrombolysis, ture review and recommendations. Am J Health Syst 41(1), 206-232. doi:10.1007/s11239-015-1310-7 Pharm, 77(11), 865-876. doi:10.1093/ajhp/zxaa059 32. Douketis, J. D., MD, FRCPC, FACP, FCCP, & Lip, G. Y., Kubitza, D., Becka, M., Zuehlsdorf, M., & Mueck, W. MD, FRCPE, FESC, FACC. (2019, August 8). Periopera(2007). Body weight has limited influence on the safetive management of patients receiving anticoaguty, tolerability, pharmacokinetics, or pharmacodylants (1031789978 790997049 L. L. Leung MD & namics of rivaroxaban (BAY 59-7939) in healthy sub1031789979 790997049 J. S. Tirnauer MD, Eds.). Rejects. J Clin Pharmacol, 47(2), 218-226. trieved November 05, 2020, from doi:10.1177/0091270006296058 https://www.uptodate.com/contents/perioperativemanagement-of-patients-receiving-anticoagulants Stangier, J., StĂ¤hle, H., Rathgen, K., Roth, W., & Shakeri-Nejad, K. (2008). Pharmacokinetics and pharmaco- 33. Shoeb, M., & Fang, M. C. (2013). Assessing bleeding risk dynamics of dabigatran etexilate, an oral direct in patients taking anticoagulants. J Thromb Thrombothrombin inhibitor, are not affected by moderate helysis, 35(3), 312-319. doi:10.1007/s11239-013-0899-7 patic impairment. J Clin Pharmacol, 48(12), 1411-1419. 34. Langer, A., & Connors, J. M. (2020). Assessing and Redoi:10.1177/0091270008324179 versing the Effect of Direct Oral Anticoagulants on Graff, J., & Harder, S. (2013). Anticoagulant therapy Coagulation. Anesthesiology, 133(1), 223-232. with the oral direct factor Xa inhibitors rivaroxaban, doi:10.1097/aln.0000000000003268 apixaban and edoxaban and the thrombin inhibitor 35. Eichinger, S. (2016). Reversing vitamin K antagonists: dabigatran etexilate in patients with hepatic impairmaking the old new again. Hematology Am Soc Hement. Clin Pharmacokinet, 52(4), 243-254. matol Educ Program, 2016(1), 605-611. doi:10.1007/s40262-013-0034-0 doi:10.1182/asheducation-2016.1.605 Bauer, K. A., MD, & Barss, V. A., MD, FACOG. (2020, 36. Reversal Agents for Commonly Used DOACs. (2019, March 26). Use of anticoagulants during pregnancy August 19). Retrieved June 29, 2020, from and postpartum (L. L. Leung MD, C. J. Lockwood MD, https://www.pharmacytimes.com/publications/Directi MHCM, & J. S. Tirnauer MD, Eds.). Retrieved August 14, ons-in-Pharmacy/2019/August2019/reversal-agents2020, from https://www-uptodatefor-commonly-used-doacs com.ezproxy.uky.edu/contents/use-of-anticoagulantsduring-pregnancy-and37. Andexanet alfa. In: Lexi-drugs online [database on the postparInternet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated tum?search=Use%20of%20anticoagulants%20during 5 Aug 2020; cited 14 Aug 2020]. Available from: %20pregnancy%20and%20postpartum&source=searc http://online.lexi.com. Subscription required to view. h_result&selectedTitle=1~150&usage_type=default&dis play_rank=1

26. Martin, K. A., Lee, C. R., Farrell, T. M., & Moll, S. (2017). Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance. Am J Med, 130(5), 517-524. doi:10.1016/j.amjmed.2016.12.033

CPE Monitor

We encourage you to check CPE Monitor to ensure you have received all 15 hours 27. Newall, F., Branchford, B., & Male, C. (2018). Anticoagu- required for licensure in Kentucky. If you lant prophylaxis and therapy in children: current chal- have any questions regarding credits, lenges and emerging issues. J Thromb Haemost, 16(2), please contact the KPhA staff immediately. 196-208. doi:10.1111/jth.13913

28. Gaasch, W. H., MD, &amp; Konkle, B. A., MD. (n.d.). Antithrombotic therapy for surgical prosthetic heart valves and surgical valve repair. Retrieved September 25, 2020, from https://www.uptodate.com/contents/antithrombotictherapy-for-surgical-prosthetic-heart-valves-andsurgical-valve-repair-indications 29. Rechenmacher, S. J., MD, & Fang, J. C., MD. (2015). Bridging Anticoagulation: Primum Non Nocere. Retrieved October 02, 2020, from https://pubmed.ncbi.nlm.nih.gov/26383727/ 30. Newall, F., Branchford, B., & Male, C. (2018). Anticoagulant prophylaxis and therapy in children: current chal-

|17| www.KPHANET.org

November 2020 — Review of Direct Acting Oral Anticoagulants

1. Which of the following medications is not a factor-Xa inhibitor?

7. Which of the following anticoagulants is a guideline recommended first-line agent for use in pregnancy

A. Rivaroxaban

A. Low molecular weight heparin

B. Apixaban

Warfarin

Apixaban

Edoxaban

D. Dabigatran

D. None of the above

2. Which of the following is an advantage of DOACs over warfa- 8. Which oral anticoagulant is recommended for patients with rin? a mechanical heart valve? A. DOACs do not have dietary restrictions

A. Apixaban

DOACs require less monitoring than warfarin

Warfarin

DOACs have less drug-drug interactions than warfarin

Dabigatran

All of the above

D. Rivaroxaban

3. DOACs...

Are easily influenced by diet

9. A patient with a high bleeding risk, experienced an interruption in apixaban therapy due to a procedure. The patient’s CrCl is 52 mL/min. How soon should DOAC therapy be resumed?

Are easily reversed by oral or IV Vitamin K1

A. 12 hours

A. Are affected by patient’s liver and renal function

D. Require extensive monitoring

24 hours

C. 48 hours 4. Which DOAC does not need to be dose-adjusted based solely D. 72 hours on kidney function (CrCl)? A. Apixaban B.

Edoxaban

10. Which of the following is not a black box warning for Andexanet Alfa?

Rivaroxaban

A. Arterial and venous thromboembolic events

D. Dabigatran 5. What is the most efficient reversal agent for warfarin? A. Subcutaneous Vitamin K B.

Intravenous Vitamin K

Fresh-Frozen Plasma

D. Ciraparantag 6. When is a reversal agent indicated? A. When patient is experiencing a life-threatening bleed B.

When patient is about to undergo invasive emergency procedure

All of the above

D. None of the above

|18| Kentucky Pharmacists Association | November/December 2020

QTC prolongation

Ischemic events

D. Cardiac arrest E.

Sudden death

This activity is a FREE service to members of the Kentucky Pharmacists Association. The fee for non-members is $30. Mail completed forms to: KPERF, 96 C Michael Davenport Blvd., Frankfort, KY 40601. Credit will be applied to your CPE Monitor Profile.

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PHARMACISTS ANSWER SHEET

November 2020 — Review of Direct Acting Oral Anticoagulants

Universal Activity #0143-0000-20-011-H01-P Name _______________________________________________ KY Lic. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 3. A B C D 5. A BC D 2. A B C D 4. A B C D 6. A B C D

7. A B C D 8. A B C D

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Information presented in the activity: Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieved the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No If yes, please explain on a separate sheet. Unmet Objectives:______________________________________________________________________________ I hereby certify that I completed this self-study program independently and without assistance from any other party. Signature ____________________________________________Completion Date___________________________ Personal NABP eProfile ID #_____________________________ Birthdate _______ (MM)_______(DD)

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Feature Article A Global Pandemic: Once a History Lesson Now a Modern-Day Reality – A Comparison Between the Spanish Flu and COVID-19 Pandemic Authors: Jessica Mattingly, 2021 PharmD Candidate; Abigail Quinlin, 2021 PharmD Candidate; Amy Priest, 2022 PharmD Candidate; Emily Frederick, PharmD, BCPS With the COVID-19 pandemic still causing global health and safety concerns and dominating news cycles, it may be difficult to recall a time the nation has ever previously been so strained by a healthcare crisis. However, this is not the first time such a large-scale pandemic has rocked the nation and likely not the last. One notable historical example of a large-scale pandemic is the 1918 influenza pandemic (also referred to as the Spanish Flu). Though over 100 years have passed since the onset of the 1918 influenza, many references and comparisons have been drawn between it and COVID-19. Though the two pandemics differ in their causative agents, they also share some parallels such as the global response to each. The Spanish influenza spread globally between 1918-1920 and was caused by the orthomyxovirus, subtype H1N1. This virus wreaked havoc initially in Europe before eventually spreading throughout the United States in “waves”1. The initial wave in the United States resulted in mass illnesses, but relatively low mortality rates that are similar to annual influenza mortality rates. As the infection rates from the first wave decreased another wave was looming. The next wave struck a few months later and spread throughout Europe. The spread of this wave was thought to be partially due to shipping goods and the subsequent contacts made upon carrier ships docking at shore. This wave contributed to the majority of infections and deaths attributable to the virus. The final wave of the pandemic struck the United States in early 1919. This final wave had a lower rate of infection than the second waved but still retained a similar mortality rate as compared to the second wave2. In total, it was estimated that the |20| Kentucky Pharmacists Association | November/December 2020

Spanish Flu lead to more than 500 million cases of infection and greater than 50 million individuals losing their lives due to the virus1. It has been postulated that the impacts of Spanish Flu could have been exacerbated by several factors including uncleanliness and overcrowding. The symptoms of infection varied based on the severity of illness, but patients often presented with symptoms such as fever, headache, nosebleed, pneumonia, encephalitis, blood-streaked urine, and coma. Those infected were also at risk of acquiring a secondary bacterial pneumonia infection that further increased the possibility of complications and increased the mortality rate1. At the time when the 1918 influenza shocked the world, science was less advanced compared to today and there were not any known vaccines or medications that were effective in mitigating it. Non-pharmacologic treatment options were conceptualized and applied in certain cases, but success was limited. For example, in China, people sprayed their houses with lime water or powder and burned rhubarb and atracytoldes rhizome to disinfect the air. Additionally, for prevention some recommended drinking soup that was made from mung bean and rock sugar several times a day. Herbal remedies were also attempted to treat infected patients. Despite these efforts, it was not until the late 1930’s that a viable vaccination to treat influenza was finally in the developmental stages but even still, an empiric formulation did not become available to the masses until 19454. Similar to the impacts of the Spanish Flu, COVID-19 has also rattled global society due to its high transmissibility and its lack of proven effective treatment option. Though similar in impact, COVID-19 differs from the Spanish Flu in its origin. COVID-19 is a respiratory infection caused by the SARS-COV-2 virus. The virus is theorized to have begun its infectious pathway via animal source at a market in Wuhan, China. This market was involved in the trade of fish and more “exotic” animals, such as bats – which is believed to be the original source of infection. The virus mutated from the form which infected the bat and was able to successfully infect humans in a mechanism that was previously never seen by the immune system. The first COVID-19 cases were reported in December 2019 and eventually spread

throughout the world. Similar to the waves of Spanish influenza infection, the COVID-19 pandemic has been manifesting in peaks and troughs of infection rates. In March of 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic5.

infection, they may still present with an array of symptoms of varying severity. Some severe cases can often result in hospitalization. Such severe disease complications may include trouble breathing, pain or pressure in the chest, new onset confusion, inability to wake or stay awake, and/or a bluish tint The initial symptoms of COVID-19 infection includto the lips or face. Upon admission to a hospital faed fever and dry cough which can progress to rescility, a patient will first be screened for symptoms piratory distress6. The CDC has published an exand then a COVID-19 test will be administered to panded symptom list that includes chills, difficulty confirm or rule out a diagnosis. There are two difbreathing, fatigue, body aches, headache, loss of ferent types of COVID-19 tests. One method of testtaste or smell, congestion, runny nose, nausea, ing screens for the presence of antibodies which vomiting, diarrhea7. Each of these symptoms is indicate a history of infection. Generally, the presused in health care facilities, inpatient and outpaence of antibodies provides protection from the tient a like, around the nation in order to screen papossibility of future infections from the same agent. tients coming in for COVID-19. However, it is currently uncertain as to whether a The virus is primarily spread through respiratory person previously infected with COVID-19 is prodroplets (usually from coughing or sneezing) that tected from future exposures, and more research is either directly or indirectly infiltrate mucous mem- needed in this realm. The other type COVID-19 test branes in the eyes, nose, or mouth. With this mode which is currently more commonly used is a viral of transmission, a person can become infected test7. This test result indicates whether a patient simply from someone coughing in their face or currently has an infection, but its accuracy levels from touching a contaminated surface and then run the risk of generating false negatives or false immediately touching their face. This transmission positives. Newer tests have been approved with pathway is referred to as aerosolized transmission better results â&#x20AC;&#x201C; 3% risk of false positives and 1.5% and is the basis for the mask mandates and hand risk of false negatives8. Consequently, lab values washing recommendations by the government and and imaging tools are often utilized in inpatient the CDC. settings when symptoms suggest the presence of COVID-19 of infection, but the test results do not. Once infected, it can take up to 14 days to exhibit symptoms, but there have been reports of sympDiagnostic imaging and laboratory values are used toms appearing in as little as two days postclinically to judge the diagnosis and resolution of exposure. Regardless of the length of the prethe infection but are not definite. Rather, these symptomatic period, during the asymptomatic pe- tools are used with clinical judgement in order to riod an infected person can still actively spread the provide the best possible treatment for patients. virus. There are even individuals who have apCertain images seen on chest x-rays include bilatpeared asymptomatic but are still capable of trans- eral multi-focal opacities or peripheral ground glass mitting infection unknowingly. In addition to being opacities which lead to areas of consolidation upon highly transmissible, COVID-19 has also proven to further resolution of the disease. Opacities are seen be particularly dangerous to patients considered to with many disease states such as bacterial or viral be high-risk. These patient populations include old- pneumonia. Though imaging studies may assist in er adults and patient with certain disease states diagnosing COVID-19, diagnostic testing and best such as cancer, chronic kidney disease (CKD), clinical judgement should be used for each patient chronic obstructive pulmonary disorder (COPD), presenting with a possible COVID-19 diagnosis. As solid organ transplant recipients, obesity, heart fail- for laboratory values in possible COVID-19 cases, ure (HF), coronary artery disease (CAD), cardiomyo- leukopenia, lymphopenia, elevated aminotransferpathies, sickle cell disease, or type 2 diabetes melli- ase, C-reactive protein, D-dimer, ferritin, and lactate tus (T2DM)7. dehydrogenase are commonly seen9. Once a person begins to show signs of COVID-19

Currently, there are no definitive treatments or vac|21| www.KPHANET.org

cinations for COVID-19 and no recommended preventative measures or post-exposure treatment, without severe inpatient disease. However, many possible treatment options have been speculated and treatment ideas for severe disease have examined medication mechanisms of action and clinical testing to determine validity and support further use. Current possible therapy regimens include the use of anticoagulation with dexamethasone 6 milligrams and use of remdesivir if the inclusion criteria are met. The NIH guidelines have recommendations for remdesivir based on the severity of symptoms. With limited supplies, remdesivir was recommended for hospitalized patients who require supplemental oxygen but are not on high flow oxygenation, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Typical therapy duration is 5 days for remdesivir and 10 days for dexamethasone. In addition to the aforementioned possible treatment options, Table 1 summarizes other theorized treatment options along with their current known efficacy levels for COVID-19 treatment and their possible patient safety concerns. COVID-19 can affect people in varying severity and has a spectrum of complications. There is a surge in prothrombic molecules, and the effect typically presents in the lungs. Lung tissue becomes damaged due to the inflammation and allows fluids to infiltrate the lungs, making it difficult to breathe. The body tries to repair the damage by synthesizing fibrotic tissue, which impairs the ability of the lungs to expand and contract. This tissue further inhibits the ability to breathe and can cause chronic impairment. Furthermore, the surge in prothrombic molecules increases the risk for thrombosis which can lead to a heart attack, stroke, pulmonary embolism, or deep vein thrombosis. These conditions can have a lifelong effect on the patient and impact their quality of life. At the time of publication (11/09/2020) the US has seen 9,913,553 cases with 237,037 deaths. The state with the highest death rate is New York with 33,439 deaths while Vermont has the least with 59 deaths. However, in terms of cases California is has the most cases (964,639) and Vermont has the least (2,392).7 Though each pandemic was caused by a different virus and over 100 years separate the two public |22| Kentucky Pharmacists Association | November/December 2020

health crises, they share many parallels. Both pandemics have disrupted normal functioning of society and have instilled fear due to lack of evidencebased treatment or prevention options available. However, in each pandemic many still have attempted to use either herbal or pharmacologic therapy in a novel way in hopes some agent will be found that may prove effective in curbing infections. Finally, it can be noted that over twenty years passed before an effective vaccine for influenza reached the market. In present time, society has far advanced in medical science and technology which likely will assist in developing a vaccine to curtail the COVID-9 pandemic, but it is imperative that diligent research and clinical trials are conducted to ensure any vaccine that reaches the market is safe and effective. References: 1.

Martini M, Gazzaniga V, Bragazzi NL, Baberis I. The spanish influenza pandemic: a lesion from history 100 years after 1918. J Prev Med Hyg. 2019; 60(1):E64-E67.

Nickol ME, Kindrachuk J. A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918-1919. BMC Infect Dis.2019; 19 (117).

Cheng KF, Leung PC. What happened in china during the 1918 influenza pandemic? Int J Infect Dis. 2017; 11(4):360-364.

4. Wallace R. Medical innovations: from the 1918 pandemic to a flu vaccine. The National WWII Museum â&#x20AC;&#x201C; New Orleans. 2020 Apr; 2020 Sept. 5.

Rico-Mesa JS, White A, Anderson AS. Outcomes in patients with COVID-19 infection taking ACEI/ARB. Curr Cardiol Rep. 2020; 22(5):31.

6. Li Y, Bai W, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020 Mar 11. [Epub ahead of print]. 7. United States COVID-19 Cases and Deaths by State. CDC. https://covid.cdc.gov/covid-datatracker/#cases_casesper100klast7days. 2020 Jan; 2020 Nov 5; 2020 Nov 5. 8. FDA â&#x20AC;&#x201C; BinaxNOW COVID-19 Ag CARD. FDA. https://www.fda.gov/media/141570/download.

Proposed Therapy

Mechanism of Action

Evidence

Concerns

No longer recommended

IL-1 and IL-6 inhibitors10

Prevents fusion to host cell membrane and blocks release of viral genome Inhibits cytokine storm

QTc prolongation Retinal toxicity Long half-lives (40 days) Infections

Mesenchymal Stem Cells9

Immunomodulary properties

Insufficient data

Infections Tumor growth Thrombus formation Administration site reactions

Vitamin C9

Antioxidant Free-radical scavenger Anti-inflammatory properties Receptor expressed on B and T cells and Antigen Presenting cells

Insufficient data

May affect point of care glucose readings

Insufficient data

Nephrocalcinosis

Zinc9

Increased concentrations efficiently impair replication in RNA viruses

Antithrombotic therapy9

Antagonize the prothrombic state

Anemia Leukopenia Ataxia Paresthesia Copper deficiency Bleeding HIT thrombocytopenia

Corticosteroids9

Inhibit cytokine storm

Remdesivir9

RNA chain termination

Insufficient data Recommend against doses above the recommended dietary allowance Recommended with no contraindications -on chronic therapy continue -prophylactic doses -treat thrombosis therapeutically Recommended on supplemental oxygen Recommended in COVID+ on supplemental Oxygen but not highflow, mechanical ventilation, or ECMO

Hydroxychloroquine Chloroquine10

Vitamin D9

Not currently studied

hyperglycemia Increase in LFTs Increase in SCr Increase PTT GI symptoms

2020 Aug; 2020 Nov. 9. 2020 NIH COVID-19 Treatment Guidelines. Published online 2020 Jul 17. Updated 2020 Jul 30. Accessed 2020 Aug 8.Kotwani A, Gandra S. Potential pharmacological agents for COVID-19. Indian J Public Health. 2020; 64(6):112-116.

|23| www.KPHANET.org

Have an idea for a continuing education article? WRITE IT! Continuing Education Article Guidelines

The following broad guidelines should guide an author to completing a continuing education article for publication in The Kentucky Pharmacist. 



Average length is 4-10 typed pages in a word processing document (Microsoft Word is preferred). Articles are generally written so that they are pertinent to both pharmacists and pharmacy technicians. If the subject matter absolutely is not pertinent to technicians, that needs to be stated clearly at the beginning of the article.



Article should begin with the goal or goals of the overall program – usually a few sentences.



Include 3 to 5 objectives using SMART and measurable verbs.



Feel free to include graphs or charts, but please submit them separately, not embedded in the text of the article.

|24| Kentucky Pharmacists Association | November/December 2020



Include a quiz over the material. Usually between 10 to 12 multiple choice questions.



Articles are reviewed for commercial bias, etc. by at least one (normally two) pharmacist reviewers.



When submitting the article, you also will be asked to fill out a financial disclosure statement to identify any financial considerations connected to your article.



Articles should address topics designed to narrow gaps between actual practice and ideal practice in pharmacy. Please see the KPhA website (www.kphanet.org) under the Education link to see previously published articles.



Articles must be submitted electronically to the KPhA director of communications and continuing education (info@kphanet.org) by the first of the month preceding publication.

December CPE Article Management of Diabetes-Related Neuropathic Pain Author: Lourdes Cross, PharmD, BCACP, CDCES and Long Phan, PharmD; Sullivan University College of Pharmacy and Health Sciences The author declare that there are no financial relationships that could be perceived as real or apparent conflicts of interest. Universal Activity #0143-0000-20-012-H01-P&T 2.5 Contact Hours Expires 12/14/23 Goal: To aid pharmacists and pharmacy technicians in understanding of current recommendations for treatment of pain associated with diabetic peripheral neuropathy and to assist with appropriate use of medications. Learning Objectives: At the conclusion of this Knowledge-based article, the reader should be able to: 1.

Describe the epidemiology of diabetic peripheral neuropathy (DPN)

Discuss pharmacologic recommendations for the management of DPN

Compare and contrast pharmacologic options for the management of DPN

Introduction

and gabapentinoid antiepileptic agents. Capsaicin is also an option, but it is generally poorly tolerated. Diabetic peripheral neuropathy (DPN) is a major In the United States, the three medications that complication of diabetes, with a reported prevaare FDA-approved are duloxetine, pregabalin, and lence of 30% in hospitalized patients and 20% in the capsaicin patch (8%). Comparative efficacy is ambulatory patients.1 As the duration of diabetes similar among the first-line medication options. A increases, so does the risk of developing neuropatwo- to three-month trial is usually required to asthy. An estimated 7% to 10% of patients newly diagsess response to initial therapy. nosed with diabetes have neuropathy, and this number increases to 50% in patients with longterm diabetes (>25 years duration).2 Patients may First-line Pharmacotherapy describe symptoms as numbness (similar to wearing gloves or socks), tingling, burning, aching, or sensitivity to touch. Peripheral neuropathy is one of Serotonin-Norepinephrine Reuptake Inhibitors the most important risk factors for amputations Duloxetine, a serotonin-norepinephrine reuptake and ulcers in people with diabetes, and it also ininhibitor (SNRI), is a first-line treatment option for creases risk for gait instability and falls. Furthermore, it may lead to insomnia, depression, anxiety, painful DPN given its efficacy, safety, and tolerabillimited mobility, and overall reduced quality of life. ity. It is also FDA-approved for use in patients with Established neuropathy is generally not reversible, major depressive disorder, generalized anxiety disso the primary goal of management is to slow pro- order, fibromyalgia, or chronic musculoskeletal gression, prevent complications, and alleviate pain. pain. The recommended initial dose of duloxetine for DPN is 60 mg daily. Lower doses may be considered when tolerability is a concern. In one systemic review which included 2,728 participants, Treatment for Neuropathic Pain duloxetine 60 mg daily compared to placebo was Management of neuropathic pain is an important effective in reducing pain by â&#x2030;Ľ50% at 12 weeks (risk component of care in patients with DPN. First-line ratio [RR] 1.73, 95% confidence interval [CI] 1.44pharmacotherapy options include antidepressants |25| www.KPHANET.org

2.08).3 Doses greater than 60 mg daily are not recommended, because they are no more efficacious and associated with increased side effects.4 Improvement in pain may be seen as early as one week after treatment.5 Venlafaxine is not as well studied as duloxetine, but doses between 150 and 225 mg daily have shown some effectiveness for DPN.6 In a randomized, placebo-controlled study that evaluated venlafaxine extended-release (ER), the pain intensity reduction at week 6 was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P<0.001 vs. placebo). The number needed to treat (NNT) for the 50% pain intensity reduction with higher dose venlafaxine was 4.5 at week 6, which is comparable to those of tricyclic antidepressants and gabapentin.7 Similar to duloxetine, venlafaxine is a good option for patients with concomitant depression or anxiety. The SNRIs are generally well tolerated. The most common side effects include nausea, dry mouth, decreased appetite, dizziness, drowsiness, fatigue, and headache. In addition, SNRIs can exacerbate restless legs syndrome. Venlafaxine exhibits more noradrenergic activity with higher doses and has been shown to cause dose-dependent increases in blood pressure. SNRIs should not be taken with other serotonin or norepinephrine reuptake inhibitors (including tricyclic antidepressants), but they can be combined with pregabalin or gabapentin. Tricyclic Antidepressants Based on the American Diabetes Association position statement for the treatment of diabetic neuropathy, tricyclic antidepressants (TCAs; including amitriptyline, nortriptyline, desipramine) are effective and recommended in the management of DPN but should be used cautiously due to the risk for cardiovascular adverse effects.6 The starting dose of amitriptyline or nortriptyline is 10 to 25 mg daily and may be gradually titrated up to 100 mg daily. Desipramine should be initiated at 25 mg daily and can be gradually increased to 200 mg daily over a few weeks. Up to 6 to 8 weeks may be needed before reasonable effects are noted by the patient.8 A lower dose is usually required for pain compared to when TCAs are used for depression.

loxetine which was a significant improvement in pain compared to baseline values (P<0.001). A systematic review found no significant differences among TCAs in analgesic efficacy.10 Because of their side effects, TCAs are generally reserved for refractory pain once alternatives have been tried first. Potential adverse reactions include anticholinergic effects (constipation, dry mouth, blurry vision, urinary retention) and orthostatic hypotension. Amitriptyline has a higher incidence of anticholinergic effects compared to desipramine and nortriptyline. TCAs should be used with caution in patients with a history of cardiovascular disease (including previous myocardial infarction, stroke, tachycardia, or conduction abnormalities). Use should be limited in older adults due to increased risk of sedation, cardiovascular events, and falls associated with dizziness and orthostasis. The TCAs may be helpful when sedation is a desired effect, such as in patients with sleep onset difficulties. Gabapentinoid Antiepileptic Agents Pregabalin is FDA-approved for the management of neuropathic pain associated with DPN. The usual starting dose of pregabalin immediate release for DPN is 75 to 150 mg daily. The immediate-release formulation should be given in two to three divided doses and increased based on response and tolerability in increments of 75 mg/day every ≥3 days based on response and tolerability (maximum 300 to 450 mg daily). Higher doses up to 600 mg daily have shown increased risk without additional benefit. The pregabalin extended-release formulation should be initiated at 165 mg daily and may be increased to a maximum dose of 330 mg daily. In one systematic review, more patients in the pregabalin group had a ≥50% reduction in pain intensity versus placebo (31% vs 25%; RR 1.3, 95% CI 1.2-1.5).9 Although not FDA-approved for DPN, data also support the use of gabapentin for reducing pain in diabetic neuropathy. In one meta-analysis, 37 studies were included to evaluate the use of oral gabapentin at daily doses of 1200 mg or more in a total of 1,277 patients with DPN.11 Gabapentin was significantly better than placebo in achieving a ≥50% pain intensity reduction (38% vs 21%; RR 1.9, 95% CI 1.52.3). The usual starting doses for gabapentin are 100 to 300 mg one to three times daily, and it can be gradually titrated to a usual effective dose of 900 to 3600 mg daily in three divided doses.

In a randomized, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine once daily for a period of 6 weeks each.9 A median pain score reduction of >50% was achieved in 55% of paPatients who have an unsatisfactory response to tients on amitriptyline and 59% of patients on du|26| Kentucky Pharmacists Association | November/December 2020

treatment with gabapentin may respond to equivalent doses of pregabalin.12 It is suggested that the analgesic action of pregabalin is 6 times that of gabapentin in terms of effectiveness in dosage conversion.13 Therefore, a patient receiving 1,800 mg of gabapentin would require 300 mg of pregabalin to achieve a comparable effect.

water and hot weather.16 Severe irritation to the eyes, mucous membranes, respiratory tract, or skin may occur due to unintended capsaicin exposure. Lidocaine

Lidocaine 5% patches are possibly effective in lessening the pain of DPN. In an open-label, 3-week study of lidocaine 5% topical patches, 70% of paGabapentin and pregabalin have similar side effects tients with DPN reported a â&#x2030;Ľ30% reduction in mean profiles, which includes somnolence, dizziness, daily pain compared with baseline values.17 Lidoataxia, peripheral edema, and weight gain. In addicaine patches should not be applied for more than tion, both require renal dose adjustments. Pregaba12 hours in a 24-hour period. Lidocaine patches may lin has a warning for those at risk of addiction or be cut without disrupting the integrity of the doshabituation. If discontinuation is desired, gabapenage form. tin or pregabalin should be withdrawn gradually. Rapid withdrawal can precipitate seizures, even in patients without a seizure history. Opioids Other Therapy Second- and third-line medications for pain associated with DPN include topical analgesics and opioids. While opioids are effective, concerns for adverse reactions and addiction limits their widespread use.

Tapentadol extended-release was approved by the FDA for the treatment of neuropathic pain associated with DPN. However, it is generally not recommended as first- or second-line therapy due to concerns for addiction and safety compared to modest pain reduction.18 Per the American Diabetes Association, the use of any opioids for chronic neuropathy carries the risk of addiction and should be avoided.18

Capsaicin Capsaicin is an option for add-on or monotherapy. Capsaicin contains a substance derived from chili peppers that desensitizes afferent sensory nerves.14 Capsaicin 0.075% cream can be gently rubbed into painful areas until thoroughly absorbed up to 4 times daily. Hands should be washed with soap and water immediately after application, unless hands are a part of the painful area. If applying to hands, patients should wait 30 minutes before washing. The high-concentration capsaicin 8% patch can be applied to painful areas of the feet for 30 minutes (up to 4 patches in a single application) every three months as needed. One systematic review found that the NNT for the high-concentration capsaicin patch is 10.64 (95% CI 7.4-19).15 The patch should only be applied by a health care provider in a wellventilated area. The area should be pretreated with a topical anesthetic such as lidocaine prior to patch application. Capsaicin patches may be cut to match the size and shape of the treatment area.

Conclusion Neuropathy is one of the leading causes of morbidity in patients with diabetes. The painful symptoms associated with diabetic neuropathy can limit function and decrease quality of life. Treatment for DPN pain includes antidepressants (SNRIs, TCAs), gabapentinoid anticonvulsants, and topical medications. The selection of a medication for DPN should be individualized based on comorbidities, drug interactions, side effects, cost, and patient preferences.

Although capsaicin has been effective in reducing pain in DPN clinical trials, many patients cannot tolerate the adverse effects, including local burning and skin irritation which is exacerbated by warm |27| www.KPHANET.org

Table 1. Pharmacotherapy of Diabetic Peripheral Neuropathy | AE: adverse effect

FDAApUsual Recommended Medication prove Comments Dose d for DPN? Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Duloxetine Yes Initial: 60 mg/day Avoid concomitant use with other serotonin or norepinephrine reuptake inhibitors (including TCAs) Maximum: 60 mg/day AE: nausea, dry mouth, decreased appetite, dizziness, drowsiness, fatigue, Venlafaxine No Initial: 37.5-75 mg/day headache (extendedMaximum: 225 mg/day release) Tricyclic Antidepressants (TCAs) AmitriptyNo Initial: 10-25 mg/day Avoid concomitant use with other serotonin or norepinephrine reuptake inhibiline tors Maximum: 150 mg/day divided in 1 to 2 doses Avoid use in geriatric population if possible; less-severe anticholinergic and sedation effects with desipramine and nortriptyline DesipraNo Initial: 12.5 mg/day mine Maximum: 250 mg/day AE: anticholinergic effects (e.g., dry mouth, urinary retention), sedation, cardiac arrythmias, orthostatic hypotension divided in 1 to 2 doses NortriptyNo Initial: 12-25 mg/day line Maximum: 100 mg/day Gabapentinoid Anticonvulsants Gabapentin No Immediate-release May be used with SNRIs or TCAs Initial: 100-300 mg 1 to 3 times daily Maximum: 1200 mg 3 times daily

Requires renal dose adjustment Pregabalin has a warning for those at risk of addiction or habituation AE: somnolence, dizziness, ataxia, lower extremity edema, weight gain

Extended-release Initial: 300 mg daily Maximum: 3600 mg/ day Pregabalin

Yes

Immediate-release Initial: 75-150 mg/day in 2 to 3 divided doses Maximum: 300 to 450 mg/day Extended-release Initial: 165 mg/day Maximum: 330 mg/day

Other Capsaicin

Yes (patc h)

Cream (0.075%)

May be used as adjunct to oral medications

Apply 4 times daily

Wash hands with soap and water immediately after applying (unless hands are part of the treatment area); if applying cream to hands, wait 30 minutes before washing hands

Patch (8%) Apply up to 4 patches to feet for 30 min every 3 months as needed Lidocaine 5% patch

AE: localized stinging, burning, itching

Apply up to 3 patches May be used as adjunct to oral medications daily for up to 12 hours AE: application-site reactions (e.g., burning sensation, discoloration, blisters, in any 24-hour period |28| Kentucky Pharmacists Association | November/December 2020 erythema)

References 1. Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia. 2000;43(8):957-973. 2.

Bansal V, Kalita J, Misra UK. Diabetic neuropathy. Postgrad Med J. 2006;82(964):95-100.

3. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane database Syst Rev. 2014;(1):CD007115. 4. Ormseth MJ, Scholz BA, Boomershine CS. Duloxetine in the management of diabetic peripheral neuropathic pain. Patient Prefer Adherence. 2011;5:343-356. 5. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1-2):109-118. 6. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154. 7. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110(3):697-706. 8. Dworkin RH, Oâ&#x20AC;&#x2122;Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237-251. 9. Kaur H, Hota D, Bhansali A, Dutta P, Bansal D, Chakrabarti A. A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial. Diabetes Care. 2011;34(4):818-822. 10. McQuay HJ, TramĂ¨r M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain. 1996;68(2-3):217-227. 11. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice ASC. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane database Syst Rev. 2014;2014(4):CD007938. 12. Stacey BR, Dworkin RH, Murphy K, Sharma U, Emir B, Griesing T. Pregabalin in the treatment of refractory neuropathic pain: results of a 15-month open-label trial. Pain Med. 2008;9(8):1202-1208. 13. Ifuku M, Iseki M, Hidaka I, Morita Y, Komatus S, Inada E. Replacement of gabapentin with pregabalin in postherpetic neuralgia therapy. Pain Med. 2011;12(7):1112-1116. 14. Chong MS, Hester J. Diabetic painful neuropathy: current and future treatment options. Drugs. 2007;67(4):569-585. 15. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173. 16. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-1765. 17. Barbano RL, Herrmann DN, Hart-Gouleau S, Pennella-Vaughan J, Lodewick PA, Dworkin RH. Effectiveness, tolerability, and impact on quality of life of the 5% lidocaine patch in diabetic polyneuropathy. Arch Neurol. 2004;61(6):914-918. 18. 11. Microvascular complications and foot care: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S135-S151.

|29| www.KPHANET.org

December 2020â&#x20AC;&#x201D;Management of Diabetes-Related Neuropathic Pain 1. In patients with a history of diabetes of more than 25 years, what is the estimated prevalence of neuropathy? A. 10% B.

25%

50%

D. 65%

2. Which is a first-line recommended agent for pain associated with diabetic peripheral neuropathy? A. Duloxetine

D. Venlafaxine 7. How often can the capsaicin 8% patch be applied for pain? A. Once weekly B.

Every 2 weeks

Every 1 month

D. Every 3 months

8. Which statement regarding capsaicin and lidocaine patches is true?

Lamotrigine

A. Only capsaicin patches (not lidocaine) can be cut before application

Sertraline

Only lidocaine patches (not capsaicin) can be cut before application

Both capsaicin and lidocaine patches can be cut before application

D. Tapentadol

3. What is the most common adverse effect of capsaicin? A. Vivid dreams B.

Hypertension

Somnolence

D. Skin irritation

4. Which medication should be avoided in a patient with a history of cardiac conduction abnormality?

D. Neither capsaicin nor lidocaine patches can be cut before application

9. Abrupt withdrawal of gabapentin may cause: A. Hypotension B.

Dizziness

Seizures

D. Bradycardia

A. Amitriptyline B.

Duloxetine

Gabapentin

D. Pregabalin

10. What is the maximum amount of time a lidocaine 5% patch can be applied to the skin? A. 8 hours B.

12 hours

5. In a patient currently receiving 3,600 mg of gabapentin, what C. 24 hours dose of pregabalin would be needed to achieve a comparaD. 72 hours ble effect? A. 100 mg B.

300 mg

600 mg

D. 900 mg

6. Which medication has an FDA-approved indication for depression and fibromyalgia? A. Amitriptyline B.

Duloxetine

Gabapentin

|30| Kentucky Pharmacists Association | November/December 2020

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With the substantial impacts of the relentless COVID-19 pandemic, telehealth services have become more prominent as healthcare providers have sought alternative options to care for their patients while reducing contact to curtail the risk of COVID19 spread.2 The shift to a more virtual climate could be a driving force to cement telepharmacy as a mainstay option in patient care. Though the need for social distancing may be one of the most relevant benefits in the use of telepharmacy currently, there are many other benefits of telepharmacy such as expanding the pharmacistâ&#x20AC;&#x2122;s role in patient Author: Amy E. Priest care and improving patient access. However, despite these possible advantages, telepharmacy also Sullivan University College of Pharmacy and Health presents several factors to consider prior to initiatSciences ing this type of service. These factors include current regulations, technology management, and poObjective: To identify clinical opportunities for phartential patient specific barriers. macists using telepharmacy methods and to identify factors to consider prior to initiating telepharma- Arguably the most significant benefit to telepharcy service. This paper will discuss advantages of us- macy practice is expanded access to care, particuing telepharmacy services such as addressing pro- larly for patients in rural settings. There is a disparivider services, expanding the scope of care in rural ty in healthcare access in rural areas which contain areas, and limiting costs for institutions. Additional- approximately 20% of the US population but only ly, this paper will discuss important potential obsta- 9% of practicing healthcare providers.1 To obtain cles that must be managed prior to starting a tele- healthcare access, some people living in remote pharmacy service. These factors include determin- areas must travel great distances. Telepharmacy provides a convenient solution for this patient poping reimbursement eligibility, establishing approulation. Instead of traveling, they could access a priate technology and security infrastructure, and provider within minutes to discuss their medicaassembling an effective team to deliver care. tions and any issues they may be experiencing. Telepharmacy Management â&#x20AC;&#x201C; Opportunities and Supporting the notion that virtual healthcare could Challenges improve access, the American Telemedicine AssociThe practice of pharmacy can be closely linked with ation has estimated that telemedicine had already the idea of innovation, especially as United States helped provide care to over 3,000 remote or underpharmacists currently advocate for likely one of served areas.1 In addition to greater access to rural their most significant advances to date: obtaining populations, telepharmacy also provides the adprovider status. The desire for provider status moti- vantage of saving travel time and expenses which vates innovative methods in the profession to furotherwise could be an adherence barrier, particuther optimize patient care and demonstrate the larly for elderly or disabled patients.3 sheer worth of a pharmacist. One example of ongoAside from improving patient access, telepharmacy ing innovation in pharmacy practice is telepharmamay also provide enhanced access to skilled pharcy. Telepharmacy is a broad term used to describe macists for rural hospitals. Some rural institutions the act of providing pharmacy care via telephone have utilized telepharmacy to extend pharmacy and other virtual technologies.1 Telepharmacy can services to a 24-hour period when they otherwise also be categorized under the larger umbrella term could not have sustained access to an onsite pharof telehealth which includes a broader scope of remacist 24 hours a day. In the institutional practice, mote healthcare practices in a variety of healthcare it is often a nurse or technician that is labelling and disciplines.1 dispensing the medications while a virtual pharma-

FEATURE Article

Telepharmacy Management â&#x20AC;&#x201C; Opportunities and Challenges

|32| Kentucky Pharmacists Association | November/December 2020

cist uses video technology to monitor the process to ensure the right medication was labelled for the right patient. The pharmacist was then also available for video counseling with the patient.3 This telepharmacy practice could be instrumental in spreading pharmacy care as one pharmacist could provide services for a few different sites. In this manner, telepharmacy could also greatly assist rural institutions in decreasing their operating costs while still providing pharmacy services 24 hours a day.

er clinical service opportunities through telepharmacy include conducting medication reconciliation and medication therapy management services (MTMs).6,7 Medication reconciliation services are commonly conducted by a pharmacist onsite prior to patient discharge. However, one facility found they were able to provide more comprehensive service by supplementing their onsite staff with telepharmacy staff. This initiative helped ensure all patients received sufficient discharge instructions and helped pharmacy staff catch medication discrepancies and potential drug interactions.7 TelepharmaAnother possible benefit for institutions implecy has also been utilized to conduct MTMs and to menting telepharmacy services, in addition to remonitor patients remotely. One company that ofduced staffing pressures, is the opportunity for fers these services described their ability to monitor quicker, more efficient medication dispensing. For patients more frequently due to telepharmacy. example, in an integrated hospital system consistWith these services, pharmacists assisted patients ing of five institutions, centralized telepharmacy with adherence problems and potential adverse services were initiated for the hospital system. reactions. Upon identifying potential issues, pharPharmacists utilized a private network to access macists were able to intervene early to help optihospital data and had pharmacy phone calls routed mize the patientâ&#x20AC;&#x2122;s care.6 to them. This arrangement freed up some of the nursing staff and was found to reduce the average Though telepharmacy presents many unique opnightly order processing time for routine orders portunities for pharmacists and benefits for pafrom 26.8 minutes to 14 minutes.4 This study tients and institutions, there are also many potendemonstrated that not only can telepharmacy help tial obstacles that may arise when trying to initiate provide pharmacy services more efficiently, but a new telepharmacy service. To ensure the telethat it also can alleviate burdens on other hospital pharmacy service operates as smooth as possible, staff. these potential barriers must be considered ahead of time and properly managed throughout the proThough there are many possible advantages for incess of providing the service. stitutions that use telepharmacy, one may question the depth of services a virtual pharmacist could One of the most significant factors that must be provide. Though it may initially seem like telephar- considered in advance of providing service is reimmacy may limit the scope of a pharmacist, there are bursement. This factor may be especially difficult as actually a variety of clinical services that have been different states currently have different regulations successfully provided through telepharmacy. One regarding telehealth services. Further complicating opportunity is for enhanced complex disease state the matter, pharmacists are not currently officially management. For example, one facility developed recognized as healthcare providers by the Centers an asthma education program and delivered it to for Medicare and Medicaid Services (CMS). Consepatients via telehealth. Clinicians virtually met with quently, this lack of designation makes it difficult patients on a regular basis to help with adherence for pharmacists to be reimbursed under traditional and to assess asthma control and found an overall fee-for-service models. However, there has been a improvement in the majority of their patientâ&#x20AC;&#x2122;s asth- recent push to move towards more value-based ma control by the end of the year-long study.5 In care models which may provide the flexibility to algeneral, telepharmacy provides a unique way to low the realm of telepharmacy to expand.1 meet patients and its convenience may allow more Nonetheless, until there is a major shift in the frequent patient-clinician interactions with ample healthcare reimbursement structure in the United opportunity for thorough counseling. States, pharmacists or institutions considering initiation of telepharmacy services must carefully exIn addition to medication counseling sessions, oth|33| www.KPHANET.org

amine their state’s policies that regulate telepharmacy practices and reimbursement. One 2016 study examined telepharmacy laws and discussed various limitations in telepharmacy in the United States. At the time, the study found that telepharmacy was authorized to some extent in 23 states. However, many states vary in the extent of telepharmacy services allowed to be provided or set other regulations that may limit telepharmacy services. For example, ten states set geographic limits and only allowed telepharmacy services in areas without a traditional pharmacy within a certain driving distance. Another limitation, six states specify that telepharmacy services can only be provided in certain types of facilities. For example, in Texas, telepharmacy service is only authorized in rural health clinics or facilities that are federal or state identified as “medically underserved”. Lastly, other potential state regulations to consider are specifications on supervision, such as how many locations a pharmacist can remotely serve at one time, and on interstate services.8 Though state regulation may be one of the most pertinent factors to address prior to initiating telepharmacy services, there are other factors regarding operation that must be considered. For example, the service is highly dependent upon technology, potentially on both the pharmacist’s and the patient’s end.7 On the patient’s side, some patients may not be equipped with the proper technology or may not be comfortable using it.3 These patient specific factors must be considered when determining the target population for the service. Additionally, video telepharmacy services would require a strong internet source which may not be available or reliable in rural areas, which are thought to be a prime market for telepharmacy. Another factor to consider is information technology (IT) support. With the service depending upon technology for its delivery, technology issues could greatly hamper the patient care experience.3 Prior to initiating telepharmacy service, one must ensure they have the proper resources to manage technology infrastructure, to handle potential issues, and to prepare an alternate mode of delivery in the instance of technology outages. Another factor related to technology is the security of patient information. Telepharmacy service will involve a significant amount of private patient information being transferred virtually.3 Management must ensure they have adequate encryption and data protection established before establishing any healthcare service, including telepharmacy. Along with reimbursement and technology factors, |34| Kentucky Pharmacists Association | November/December 2020

personnel factors must also be considered to ensure staff members are sufficient in quantity and properly trained to manage the service. Leadership structure and the roles each staff member occupy should also be examined. One possible consideration in leadership structure is implementing a coordinator role in the telepharmacy service. One study examined a telehealth model that included an interprofessional team with an “interprofessional care coordinator”. This coordinator was key to the program’s success in that they helped connect staff members and helped acclimate patients to the virtual care process. With these essential actions, the study found that the coordinator was an essential player in keeping the service running smoothly and in increasing staff members’ confidence in the program’s viability.9 Delegating another person to function solely to connect staff members and to manage daily operations could be a vital component to ensuring optimal telepharmacy operations. Telepharmacy is a novel extension for pharmacy services and may be discussed for mainstream care even more now in our virtual climate than ever before. However, aside from today’s shift to a virtual climate, there are many other potential advantages to using telepharmacy as an alternative means of patient care. Telepharmacy can help improve access to rural areas or areas with provider shortages and can help institutions limit costs. Additionally, there are many patient care opportunities for pharmacist through telepharmacy including expanded counseling sessions and complex disease state management. However, prior to initiating a new telepharmacy service one must consider potential barriers to successfully delivering that service, such as technology difficulties and reimbursement hurdles. Perhaps most important is considering the team assembled to deliver the service. A comprehensive team of experts will help ensure the patient is receiving the best possible care, regardless of the mode through which it is delivered.

References 1.

website. https://www.pharmacytimes.com/publications/i ssue/2020/April2020/telehealth-offers-myriadunique-opportunities-for-pharmacists. Published 2020 April; accessed 2020 Oct 30.

Littauer SL, Dixon DL, Mishra VK, Sisson EM, Salgado TM. Pharmacists providing care in the outpatient setting through telemedicine models: a narrative review. Pharm Pract (Granda). 2017; 7. Baldoni S, Amenta F, Ricci G. Telepharmacy ser15(4):1134. doi:10.18549/PharmPract.2017.04.1134 vices: present status and future perspectives: A 2. Wosik J, Fudim M, Cameron B, et al. Telehealth review. Medicina (Kaunas). 2019; 55(7): 327. transformation: COVID-19 and the rise of virtual doi:10.3390/medicina55070327 care. JAMIA Open. 2020; 27(6): 957-962. 8. Tzanetakos G, Ullrich F, Mueller K. Telepharmacy doi.org/10.1093/jamia/ocaa067 rules and statutes: A 50 state survey. Am J Med 3. Poudel A, Nissen LM. Telepharmacy: a pharmaRes. 2018; 5(2): 7-23. doi:10.22381/AJMR5220181 cistâ&#x20AC;&#x2122;s perspective on the clinical benefits and 9. Taylor AM, Bingham J, Schussel K, et al. Intechallenges. Integr Pharm Res Pract. 2016; 5:75grating innovative telehealth solutions into an 82. doi.org/10.2147/IPRP.S101685 interprofessional team-delivered chronic care 4. Garrelts JC, Gagnon M, Eisenberg C, Moerer, J, management pilot program. J Manag Care Carrithers J. Impact of telepharmacy in a multiSpec Pharm. 2018; 24(8): 813-818. hospital health system. Am J Health Syst doi.org/10.18553/jmcp.2018.24.8.813 Pharm. 2010; 67(17): 1456-1462. doi:10.2146/ajhp090670. 5.

Brown W, Scott D, Friesner D, Schmitz T. Impact of telepharmacy services as a way to increase access to asthma care. J Asthma. 2017; 54(9): 961-967. doi:10.1080/02770903.2017.1281292.

6. Gershman J. Telehealth offer myriad unique opportunities for pharmacists. Pharmacy Times

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Welcome new Members Weâ&#x20AC;&#x2122;re so happy to have you! The list reflects new memberships received from September 1, 2020â&#x20AC;&#x201D; October 31, 2020.

If you see one of these new members, please welcome them to the KPhA family! Dale Scherzer, Hermitage, TN Associate Member

Robert Sparkman, London, KY Pharmacist Member

Evin Vann, Glasgow, KY Senior Pharmacist

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KPhA BOARD OF DIRECTORS

KPERF BOARD OF DIRECTORS

Don Kupper, Louisville donku.ulh@gmail.com

Chair

Bob Oakley, Louisville rsoakley21@gmail.com

Chair

Joel Thornbury, Pikeville jthorn6@gmail.com

President

Secretary

Cathy Hanna, Lexington channa@apscnet.com

President-Elect

Clark Kebodeaux, Lexington clark.kebodeaux@uky.edu

Treasurer

Brooke Hudspeth, Lexington brooke.hudspeth@uky.edu

Secretary

Chris Killmeier, Louisville cdkillmeier@hotmail.com

Treasurer

Joel Thornbury, Pikeville jthorn6@gmail.com

President, KPhA

Lewis Wilkerson, Frankfort rphs2@aol.com

Past President Representative

Kevin Lamping, Lexington kevin.lamping@twc.com Paul Easley, Louisville rpeasley@bellsouth.net

Directors Ronnah Alexander, Providence ralexander@hfchc.net

Sarah Lawrence, Louisville slawrence@sullivan.edu

Jessika Chilton, Beaver Dam jessikachilton@ymail.com

Pat Mattingly, Lebanon pat@patspharmacy.com

Kyle Harris, London kyleharrispharmd@yahoo.com Jacob Barnett, Lexington jacobbarnett15@gmail.com

University of Kentucky Student Representative

Sa,m Willett Interim Executive Director swillett@kphanet.org

Chad Corum, Manchester pharmdky21@gmail.com

Sarah Franklin Director of Communications & Continuing Education sarah@kphanet.org

Cassy Hobbs, Louisville cbeyerle01@gmail.com Thao Le Batovsky, Louisville tle3380@my.sullivan.edu

KPhA Staff

Sullivan University Student Representative

Jeff Mills, Louisville jeff.mills@nortonhealthcare.org Martika Martin, Owensboro Speaker of the House 12marmar@gmail.com Nathan Hughes, Louisville Vice Speaker of the House njhughes1980@gmail.com Trevor Ray, Caneyville trevor@midwaypharmacy.com Cory Smith, Barbourville corysmith6155@gmail.com Misty Stutz, Crestwood mstutz@sullivan.edu

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Angela Gibson Director of Finance & Administrative Services agibson@kphanet.org Jody Jaggers, PharmD Director of Public Health jjaggers@kphanet.org Kristen Blankenbecler, PharmD Director of Clinical Outreach kristen@kphanet.org Michele Pinkston, PharmD, BCGP Director of Emergency Preparedness michele@kphanet.org Lisa Atha Office Assistant/Member Services Coordinator latha@kphanet.org

“When you think about the problems our profession faces, think in terms of the future as well as the present. Think in terms of what you can do to improve the profession as well as yourself.” -From The Kentucky Pharmacist, December 1970 Volume XXXIII, Number 12

Frequently Called and Contacted Kentucky Board of Pharmacy

Kentucky Society of Health-System Pharmacists

(703) 683-8200 www.ncpanet.org

P.O. Box 4961

info@ncpanet.org

(502) 564-7910

Louisville, KY 40204 (502) 456-1851 x2 www.kshp.org info@kshp.org

www.pharmacy.ky.gov

Kentucky Regional Poison Center

Pharmacy Technician Certification Board (PTCB)

(800) 222-1222

National Association of Chain Drug Stores (NACDS) 1776 Wilson Blvd., Suite 200 Arlington, VA 22209 www.nacds.org 703-549-3001

State Office Building Annex, Ste. 300 125 Holmes Street Frankfort, KY 40601

2215 Constitution Avenue

American Pharmacists Association (APhA)

Washington, DC 20037-2985

2215 Constitution Avenue NW

(800) 363-8012

Washington, DC 20037-2985

www.ptcb.org

(800) 237-2742 www.aphanet.org National Community Pharmacists Association (NCPA) 100 Daingerfield Road Alexandria, VA 22314

KPhA/KPERF HEADQUARTERS 96 C Michael Davenport Blvd. Frankfort, KY 40601 502.227.2303 (Phone) 502.227.2258 (Fax) info@kphanet.org www.kphanet.org www.facebook.com/KyPharmAssoc www.twitter.com/KyPharmAssoc www.youtube.com/KyPharmAssoc |45| www.KPHANET.org

THE

Kentucky PHARMACIST 96 C Michael Davenport Blvd. Frankfort, KY 40601

https://cmppharma.com/

The Kentucky Pharmacist- - November/December 2020

Articles inside

New KPhA Members

PTCB

APMS

November CE Article

and Challenges

December CE Article

Turning Tragedy into Giving Back