Coronavirus (COVID-19) Resources For Pharmacists

Rose Nor Rose Nor
May 27, 2020 - 22:57 Updated: Feb 25, 2022 - 23:26
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Coronavirus (COVID-19) Resources For Pharmacists

This webpage is dedicated towards providing coronavirus (COVID-19) resources for pharmacists.

 

Many pharmacists across the world are working hard to keep up with therapeutic options for coronavirus / SARS-CoV-2 / COVID-19. This webpage was created to provide insights and resources for pharmacists helping to manage this pandemic. Take note that updates to the page will be made periodically as permitted and the content here may not be completely up-to-date as the situation is evolving quickly. Also beware that much of the data identified below is of relatively poor quality in terms of utility for determining what should be done in clinical practice.

Additionally, there are many potential COVID-19 therapies, I list several at the bottom, but do not discuss them in depth. Some of these can potentially lessen the cytokine storm associated with COVID-19 and help with managing acute respiratory distress syndrome (ARDS).

MOST IMPORTANTLY: Thus far no antiviral drug has been proven to work against COVID-19 in humans, although many randomized controlled trials are ongoing. There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19. Inclusion in this webpage is not an endorsement for use of any of these drugs for COVID-19.

To see what is new look for the ✓ symbol, we will be adding this to new material and removing it from older material as we keep updating the page. Use CTRL+F and search for it to find what is new.

If you have a resource that is helpful and reliable, but not posted here, send it to me: IDstewardship@gmail.com or @IDstewardship on Twitter.

General COVID-19 Resources

Institutional, Governmental & Society COVID-19 Treatment Guidelines

COVID-19 Resource Centers

COVID-19 Oriented Data Tracking Resources

COVID-19 Symptom Analysis

General Notes on COVID-19

Remdesivir for COVID-19: Resources & Notes

  • Remdesivir (RDV, GS-5734, Veklury) is a direct acting nucleoside RNA polymerase inhibitor and antiviral drug developed by Gilead Sciences
    • It is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to the active nucleoside triphosphate metabolite. Remdesivir triphosphate acts as an analog of ATP and competes with natural ATP substrate for incorporation into RNA chains by the SARS-CoV-2 RNA-dependent polymerase, which results in delayed chain termination during replication of viral RNA.
      • Remdesivir was granted FDA Emergency Use Authorization (EUA) on May 1, 2020
        • Detailed EUA information is here
  • Remdesivir fact sheet for healthcare providers from Gilead is here
  • Has activity against Ebola virus, MERS, and SARS
  • The optimal duration of treatment for COVID-19 is unknown.
    • Under the EUA the dose is broken down for adults and pediatrics
      • The suggested dose for adults and pediatric patients weighing ≥40 kg requiring invasive mechanical ventilation and/or ECMO is a single loading dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 9 days (days 2 through 10).
      • The suggested dose for adults and pediatric patients weighing ≥40 kg not requiring invasive mechanical ventilation and/or ECMO is a single dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 4 days (days 2 through 5). If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
        • See here for full dosing information provided by Gilead
    • Not recommended for eGFR falls below 30 mL/min (the SBECD excipient can accumulate)
    • Not recommended to be continued if ALT goes above 5x the upper limit of normal
  • There are limited data on RDV drug-drug interactions, but there may be interactions via the liver
    • In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP.
  • Remdesivir can be acquired from Gilead for compassionate use for COVID-19 otherwise it appears it will be distributed by AmerisourceBergen at the direction of the United States Government
    • Email to contact Gilead: coronavirus.response@gilead.com
    • AmerisourceBergen Remdesivir line: 1-877-987-4987
  • Remdesivir for the Treatment of Covid-19 — Preliminary Report ✓
    • Included 1,063 patients randomized and found remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection
  • Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
    • In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits
  • Compassionate Use of Remdesivir for Patients with Severe Covid-19
    • Reports on 61 patients given remdesivir and does not have a comparator group
  • Compassionate program has been put on hold with the exception of pregnant people and people below 18 years of age, they are expected to activate an expanded access pathway in the near future
  • In preparing to request investigational remdesivir, collecting the following information ahead of time may be helpful:
    • Prescriber name, address, email, and phone number associated with the treatment center
    • Professional designation (ie, MD) or qualifications of requester including medical license number
    • Institution/ hospital name, address, email, and phone number
    • Shipping information (including pharmacy hours)
    • Patient case information, including previous or current treatments and clinical status
  • There are many exclusion criteria for remdesivir
  • Remdesivir clinical trials
  • Gilead Announces Approval of Veklury® (remdesivir) in Japan for Patients With Severe COVID-19

Hydroxychloroquine/ Chloroquine Resources and Notes for COVID-19

Hydroxychloroquine (Plaquenil) for COVID-19: Resources & Notes

Chloroquine-specific Resources & Notes for COVID-19

Lopinavir/ritonavir (Kaletra, LPV/r) for COVID-19: Resources & Notes

  • Lopinavir is a protease inhibitor that blocks viral replication by inhibiting the coronavirus main proteinase (3CLpro) which has a vital role in polyprotein processing and virus maturation
  • Ritonavir inhibits CYP3A4 and “boosts” the concentration of lopinavir, it also has some antiviral activity
  • Data suggests LPV/r should not be used mono therapy for severe COVID-19
  • Lopinavir/ritonavir in COVID-19 patients: maybe yes, but at what dose?
  • Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial
    • In this assessment of 127 patients the authors conclude that triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19.
  • LPV/r may be effective when used in combination with other drugs versus COVID-19, but more data on this is needed and in general LPV/r appears to be falling out of favor as a potential COVID-19 therapy
  • Beware drug-drug interactions as ritonavir is a CYP enzyme inhibitor (will increase levels of other drugs)
  • Consider avoiding for patients with liver or cardiac disease
  • LPV/r comes in an oral solution, but it may not be available during times of high demand, so people may consider crushing the capsules
    • Pharmacokinetics of Lopinavir/Ritonavir Crushed versus Whole Tablets in Children
      • Crushing LPV/r can reduce the AUC by 50%
      • Increasing the LPV/r dose by 50% to compensate would mean a considerable amount of ritonavir, which may cause considerable drug-drug interactions
        • Cushing LPV/r has shown to reduce exposure to both lopinavir and ritonavir, so the increase in ritonavir may not be clinically relevant
    • From a colleague (paraphrased):
      • We may be able to use information from venetoclax (Venclexta), which like LPV/r has a film coated tablet
        • For venetoclax we dissolve the tablet into a slurry in a syringe to reduce the risk of losing drug in a crusher or amber vial. It can take up to 20 mins (per patient report) to get the drug to dissolve. The ICU nurses have not had issues with getting ventoclax surry down NG tubes, but floor nurses did report issues (potential it was not administered immediately?). We also did the tablet slurry in a syringe to reduce exposure to compounding staff.
        • This approach can avoid the use of preservatives
          • This briefing includes  information on making a pediatric venetoclax solution, notes avoiding preservatives and potential issues with stability
        • Stability data is lacking, consider immediate use
          • From the above referenced article: “Disruption of the extrude matrix environment may adversely impact this formulation affect. The crushing of the pill leaves part of the drug(s) on the walls of the container or crushing device, and the transfer of the crushed substance to the food or liquid for mixing may also generate loss of the active drug.”
  • The dose and duration I have seen recommended is LPV/r 400-100 mg BID x14 days
  • The University of Michigan COVID-19 guidance document recommends:
    • Adult dosing: 400 mg-100 mg PO BID
    • Pediatric dosing:
      • 14 days to 6 months old: lopinavir component 16 mg/kg PO BID
      • 6 months to 18 years:
        • 15-25 kg: 200 mg-50 mg PO BID
        • 26-35 kg: 300 mg-75 mg PO BID
        • >35 kg: 400 mg-100 mg PO BID
  • LPV/r oral solution has a high alcohol content and tastes terrible, which can be an issue for children in particular
  • Consider HIV testing prior to initiating therapy
  • Some clinicians are combing LPV/r with ribavirin
  • Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore
    • Includes 5 patients treated with LPV/r for COVID-19
    • None died
    • 3 of 5 developed abnormal liver test results
  • There are pre-SARS-CoV-2 publications supporting activity of LPV/r versus SARS
  • Kaletra Package Insert (tablet & oral solution)

Tocilizumab (Actemra) for COVID-19: Resources & Notes

List of Other Potential Therapies

Anticipated COVID-19 Literature

COVID-19 Literature

Other COVID-19 Webpages & Resources

DISCLAIMER: The views expressed in this article represent that of the author and do not necessarily reflect the position or policy of any previous, current, or potential future employers or other organizations in which he serves.