VSHP December Newsletter
2021 Spring Seminar Call for Presentation Proposals
2021 Virtual Spring Seminar

VSHP is accepting speaker proposals that will provide quality continuing education to our members. Please submit your completed proposal form to contact@vshp.org by Friday, January 8.

Presenters will need to schedule a time to record their session as well as be available during their session time for live Q&A. Also presenters will need to be flexible as we work through a fully virtual meeting.
Additionally, the Education Committee is interested in specific request for proposals that are focused on pharmacy technicians.

Mentorship Committee Book Club: Black Man in a White Coat

The next book club will be January 13, 2021 at 19:00. We will be discussing Black Man in a White Coat: A Doctor’s Reflection on Race and Medicine by Damon Tweedy. This was the book with the 2nd most interest based on the initial member survey (missing first place by only one vote)!

The book club entails a 1-hour online call, where members will be able to get to know each other and discuss the selected book. All members (students, technicians, etc.) welcome! VSHP Book Club will be held at 19:00 on the 2nd Wednesday of every 3rd month (January, April, July, October)
RSVP: 
 
After registering, you will receive a confirmation email containing information about joining the meeting.
Emergency Use Authorization: Bamlanivimab
Dan V. Buth, VCU School of Pharmacy PharmD Candidate, 2021
Alexis Crawford, PharmD, BCPS, BCCCP, VCU School of Pharmacy
              In November of 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow for the use of bamlanivimab (LY-CoV555). Currently, this is an unapproved product but is authorized in the treatment of mild to moderate coronavirus disease 2019 (COVID- 19).1
EUA or Emergency Use Authorization is a guidance document released by the FDA to outline the availability of medical countermeasures (MCM). These agents or products can only be authorized for use after justification from the secretary for the Department of Health and Human Services. MCMs can include unapproved agents or products to diagnose, treat, or prevent serious or life-threatening diseases or conditions involving chemical, biological, radiological, and nuclear (CBRN) agents. Multiple EUAs can be issued to meet the needs of the current state of affairs.2
Bamlanivimab is a human immunoglobulin G-1 (IgG1) monoclonal antibody that neutralizes the spike protein of SARS-CoV-2 which causes COVID-19. This helps to block the viral attachment to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is said to be a binding site for SARS-CoV-2. Bamlanivimab is most efficacious if administered as soon as possible following a positive result of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.1
The United States government has purchased 300,000 doses of bamlanivimab and is allocating doses based on the confirmed COVID-19 cases in each state. It is important to note that although the drug itself will not have out-of-pocket costs, healthcare facilities may elect to charge a fee to prepare and administer the product. Each week, the state health departments will allocate doses by choosing facilities that are most accessible and most effective in minimizing infection transmission. If it is later determined that more doses are needed, the government can purchase up to 650,000 additional doses through the end of June 2021.3
             The EUA that permits the use of bamlanivimab has imposed stringent inclusion criterion. Generally, bamlanivimab is for the treatment of mild to moderate COVID-19 in patients 12 years and older and at least 40 kg with a positive result of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe and or hospitalization.1 High risk patients are described in Table 1. Bamlanivimab can be used in patients hospitalized for reasons other than COVID-19 as long as they met the general criteria outlined in the EUA. Dosing recommendation for bamlanivimab is 700 mg in normal saline bringing the total infusion volume to 200 mL.3

Table 1: High Risk Criteria for Use of Bamlanivimab3
High risk for progressing to severe COVID-19 and/or hospitalization is defined as patients who meet at least one of the following criteria:
       Have a body mass index (BMI) ≥ 35
       Have chronic kidney disease
       Have diabetes
       Have immunosuppressive disease
       Are currently receiving immunosuppressive treatment
       Are ≥ 65 years of age
       Are ≥ 55 years of age AND have
       cardiovascular disease, OR
       hypertension, OR
       chronic obstructive pulmonary disease/other chronic respiratory disease
       Are 12 – 17 years of age AND have
       BMI ≥ 85th percentile for their age and gender based on CDC growth charts, OR
       sickle cell disease, OR
       congenital or acquired heart disease, OR
       neurodevelopmental disorders, for example, cerebral palsy, OR
       a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
       asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
             Bamlanivimab has not been authorized for use in patients who are hospitalized due to COVID-19, require oxygen therapy due to COVID-19, or require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.1
              In the SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 (BLAZE-1) trial, 452 participants were randomly assigned to receive bamlanivimab 700 mg, 2800 mg, 7000 mg, or placebo. Participants of this Phase 2 trial were at least 18 years old at the time of randomization, were not hospitalized, and had one or more mild or moderate COVID-19 symptoms. Patients were randomized to receive an infusion of bamlanivimab or placebo within three days of the first positive SARS-CoV-2 test results. The primary and secondary outcomes are described in Tables 2 and 3 (see end of article). From the trial, it was determined that the 2800 mg and 7000 mg doses produced no meaningful differences in viral load and clinical outcomes when compared to the 700 mg dose. All three doses demonstrated a flat exposure-response relationship in efficacy.4
               In this Phase 2 trial, patients were followed for at least 28 days following treatment. Adverse events occurred in 23% of patients in the bamlanivimab arm and 26% of patients in the placebo arm. Adverse events include nausea, diarrhea, dizziness, headache, pruritus, and vomiting. Serious adverse events occurred in one patient in the placebo arm and in no patients in the bamlanivimab arm.1
Bamlanivimab is preservative-free and must be administered within 24 hours when refrigerated and 7 hours if at room temperature; this time must also include administration time. The minimum infusion time is 60 minutes at a rate of 200 mL/hr. A polyvinyl chloride (PVC) infusion set containing a 0.20/0.22 micron in-line polyethersulfone (PES) filter must be used during administration. Each healthcare facility will have to determine best practices on how to administer this agent since this drug will likely be administered in an outpatient health care setting. Patients must be monitored during administration and for up to one hour following treatment. Providers must have immediate access to medication to treat anaphylaxis or a severe infusion reaction.1
               In order to mitigate the risks of using bamlanivimab, requirements must be met before use. Bamlanivimab can only be used in the treatment of mild to moderate COVID-19 in patients 12 years and older and at least 40 kg with a positive result of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe and or hospitalization. Healthcare providers must communicate information consistent with the “Fact Sheet for Patients, Parents, and Caregivers” prior to the patient receiving bamlanivimab. Patients need to be informed by their healthcare provider that bamlanivimab is an unapproved drug and discuss alternative agents to bamlanivimab. Currently, casirivimab plus imdevimab are authorized for use by another EUA to treat patients in a similar condition. Lastly, healthcare providers must report all medication errors and serious adverse events within seven days of onset to FDA MedWatch and provide a copy to Eli Lilly.1
               Currently, there is only one agent that has been FDA approved in the treatment of COVID-19. Remdesivir is only indicated for the treatment of COVID-19 patients requiring hospitalization.5 Bamlanivimab, under EUA, has been authorized by the FDA for treatment of mild to moderate COVID-19 in high-risk patients. Pharmacists, as well as the rest of the healthcare team, should be aware of the authorized use indications for bamlanivimab in order to select appropriate high-risk patients to receive the medication.
 
References:
  1. Fact sheet for healthcare providers: emergency use authorization (EUA) of bamlanivimab. U.S. Food and Drug Administration. https://www.fda.gov/media/143603/download. Accessed November 20, 2020.
  2. Emergency Use Authorization of Medical Products. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities. Accessed November 28, 2020.
  3. Frequently Asked Questions on the Emergency Use Authorization for Bamlanivimab. U.S. Food and Drug Administration. https://www.fda.gov/media/143605/download. Accessed November 28, 2020.
  4. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients With Covid-19 [Epub ahead of print October 28, 2020]. N Engl J Med. 2020.
  5. VEKLURY® (remdesivir) [package insert]. Foster City, CA:Gilead Sciences, Inc., October 2020.
Resources to Determine Beyond Use Date
Valerie Brooks, PharmD Candidate 2021 and Akeem Bale, RPh, PharmD, BCPS, MS

The beyond-use date (BUD) is used to identify the time a medication must be used before it is at risk for chemical degradation, contamination, or permeability of the packaging 1. To ensure that patients receive safe and effective medications, all medical personnel must abide by the BUD often determined by the pharmacy. While completing an Institutional APPE Rotation at Riverside Regional Medical Center, my preceptor and I realized a few members of the nursing staff were uncertain about BUD assessment and determination. Using resources available, such as USP <797>, the Center for Disease Control (CDC), and medication package inserts will ensure optimal stability and sterility of medications administered to patients.

General storage conditions
BUD must be used when manipulating a vial or changing storage conditions. This information can typically be found within the package insert. For example, the package insert for rocuronium defines the BUD as 60 days when storage conditions change from refrigerated to room temperature 2.
According to the CDC, single-use vials should only be punctured once and never used for multiple patients 3. Usually, single-use vials are classified as immediate use Compounded Sterile Preparations (CSP) and are used within 1 hour of manipulation 1. Multiple-use vials may be more difficult to determine the BUD. If the package insert does not fully define the BUD for a multiple-use vial, 28 days could be used. This is because the FDA requires all multiple-use vials to have data showing stability of the product for at least 28 days 4. There are many exceptions that may have a BUD of less than 28 days, so it is imperative to check the package insert and literature beforehand.
Assessment when compounding
           BUD must be assigned to all compounded medications based on stability and sterility. To fully understand materials available and appropriately determine the BUD of compounded medications, a step-wise process was created.

1.     Research Stability Data-
Medication stability is defined as the extent to which a medication retains the same properties and characteristics possessed at the time it is manufactured 5. Stability data is typically detailed in the package insert and can vary due to manipulation or, as previously mentioned, a change in storage condition. If the package insert is unavailable, supporting literature may be used instead.

2.     Research Sterility Data-
Factors that affect medication sterility include probability of microbial growth. Current USP <797> guidelines classify compounded medications within 3 levels to identify risk of microbial contamination 1. Compounding personnel are required to determine the appropriate risk level, which corelates to a suggested BUD based on risk level and storage setting. Low risk, medium risk, and high risk are the potential categories. The table at the end of the article classifies each risk level, the BUD, and examples of products in each risk category.

3.     Always use the shortest time available as the BUD!
If a medication has stability data claiming it is stable for 30 days, however it is a high risk compound and only sterile for 3 days the BUD would be 3 days.
           
In closing, BUD determination is important in order to assure patients are receiving stable and sterile medications. Appropriate determination of BUD are evaluated and checked by accrediting agencies, for example the DNV, and lack of adequate dating could lead to citations. Quickly referring to manufacturers’ data, the CDC, and the current USP <797> could enable pharmacists to ensure correct BUD are used, and patients are receiving stable and sterile medication.

Resources used-
1.     USP <797>: Guidebook to Pharmaceutical Compounding: Sterile Preparations. Rockville, MD: United States Pharmacopeia Convention; 2008. 
2.     Rocuronium - Food and Drug Administration. (2008, November). Retrieved August 28, 2020, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/078717s000lbl.pdf
3.     Questions about Single-dose/Single-use Vials. (2019, June 20). Acced August 28, 2020, from https://www.cdc.gov/injectionsafety/providers/provider_faqs_singlevials.html
4.     Kienle, Patricia. Understanding Beyond-Use Dating for Compounded Sterile Preparations. pppmag.com. Pharmacy Purchasing and Products. Published March 2007. Accessed October 3, 2020 from https://www.pppmag.com/documents/V4N3/p2_4_5.pdf
5.     Drug Stability. Drug Stability - an overview | ScienceDirect Topics. Accessed October 3, 2020, from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/drug-stability.
6.     ASHP Guidelines on Compounding Sterile Preparations. Best Practices. Accessed October 3, 2020, from 2019:112-131.doi:10.37573/9781585286560.041. 
Members Spotlight
VSHP and ASHP Past President R. David Anderson reflects on his first 95 years in the December 15, 2020 issue of AJHP. See article: https://academic.oup.com/ajhp/article/77/24/2037/6020050

Did You Know...

If you were unable to attend our live webinars, you can view them at http://vshp.org/Webinars
 
There are 2 options for viewing-one with one hour of pharmacist or pharmacy technician CE credit ($10 CE processing fee) and one without CE.
Clinical Writing Opportunities
As a new year of APPE rotations begin, writing a clinical article for the VSHP newsletter is a great way for students to get publication experience. As preceptors we can co-author these articles with our students, engage them in the writing process, and enhance their rotation experiences. Topics can be anything related to hospital-system pharmacy. Examples include (but are not limited to): new drug updates, national policy updates for hospital pharmacy, guideline updates, therapeutics reviews, and clinical controversies. Articles are generally 1-3 pages in length, and can include tables and figures. Interested member and students should email Steve Glass, contact@vshp.org for more details.