In this episode, I’ll discuss pharmacy-related COVID-19 updates.
Hydroxychloroquine and chloroquine FDA Emergency Use Authorization
The FDA has issued an Emergency Use Authorization for hydroxychloroquine and chloroquine to be used in patients with COVID-19. The FDA has also prepared patient and health care provider fact sheets. If you are dispensing either of these medications from supplies from the strategic national stockpile please review the healthcare provider fact sheets as there are several mandatory items that must be completed.
As pharmacists would be sure to realize, this is not the same as an FDA approved use in the traditional sense. This is emergency authorization for an unapproved use. The FDA strongly encourages the conduct and participation in randomized controlled clinical trials that may produce evidence concerning the effectiveness of these medications in treating COVID-19. The authorization is based on the limited in vitro, case series, and anecdotal reports of these medications and is subject to change pending higher levels of evidence.
The main purpose of the FDA in issuing the EUA is to facilitate the availability of chloroquine and hydroxychloroquine during the COVID-19 pandemic to treat patients for whom a clinical trial is not available, or participation is not feasible. This will be handled through the strategic national stockpile and distribution to states by FEMA.
The way for hospitals to access this supply of medications is by making a request through your local or state health department.
One possible immediate benefit of this authorization is that the recommended frequency for hydroxychloroquine is for it to be administered once daily. This should help cut down on unnecessary med passes by nurses that would otherwise consume PPE.
Hydroxychloroquine and azithromycin QTc update
There is now more information on how French authors of the hydroxychloroquine+azithromycin study have evaluated the QTc risk of this combination.
The same authors of the 1st study of these medications have a new observational study of 80 patients receiving hydroxychloroquine + azithromycin (there is no control group).
In the methods they detail how the QTc risk:benefit was evaluated:
- Twelve-lead electrocardiograms (ECG) were performed on each patient before treatment and two days after treatment began.
- The treatment was either not started or discontinued when the QTc using Bazett’s formula was greater than 500 ms and the risk-benefit ratio was estimated to be between 460 and 500 ms. I assume this statement about risk-benefit is unclear due to a translation from French to English; I take it to mean that if the QTc was 460-500 an individualized risk:benefit analysis would be done to decide what course of action to take.
- The treatment was not started when the ECG showed patterns suggesting a channelopathy and the risk-benefit ratio was discussed when it showed other significant abnormalities (i.e., pathological Q waves, left ventricular hypertrophy, left bundle branch block).
- In addition, any drug potentially prolonging the QT interval was discontinued during treatment.
As with the first study, no details on the QTc intervals of the patients in the study were included.
For more on how to evaluate the unknown risk of QTc interaction between hydroxychloroquine and azithromycin, listen to episode 488.
It is hard to do a risk:benefit analysis when the benefit of the medications is based on in vitro data, a small case-control study and an observational study without a control group. It is also equally as hard to tell a patient that a treatment popularized in the media cannot be given to them due to an unknown risk of QTc prolongation. My inclination is to use the combination in most patients, checking ECGs daily as resources allow in those who may be at a higher risk of QTc prolongation. If the QTc risk for an individual patient is too high I would consider either dropping azithromycin or pursuing access to remdesivir.
Remdesivir moves to expanded access for most patients
There is now an official expanded access trial for remdesivir on clinicaltrials.gov. This is now Gilead’s preferred method to provide access to remdesivir. This is not a placebo-controlled trial; every patient enrolled receives remdesivir.
Inclusion Criteria:
-Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (participants ≥ 18 years of age)
-Hospitalized with confirmed SARS-CoV2 by polymerase chain reaction (PCR) or known contact of confirmed case with syndrome consistent with coronavirus disease (COVID-19) with PCR pending
-Requiring invasive mechanical ventilation (e.g., via endotracheal intubation or tracheostomy)
-Adequate renal function with estimated glomerular filtration rate (eGRF) ≥ 30 ml/min by local laboratory measure
-Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) by local laboratory measure
Exclusion Criteria:
-Evidence of multiorgan failure
-Pressor requirement to maintain blood pressure
-Renal failure (eGRF less than 30 mL/min or dialysis or continuous Veno-Venous Hemofiltration)
-Pregnancy
Contact Information: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com
Even though pregnancy and pediatrics are excluded under this trial, the compassionate use method on Gilead’s website still states those patients will be considered for access.
Enteral tube administration of hydroxychloroquine
Hydroxychloroquine tablets are labeled “do not crush”
A Belgian guideline on the treatment of COVID-19 recommends crushing hydroxychloroquine tablets.
I am not sure why the hydroxychloroquine tablets are labeled “do not crush” as there are studies that provide stability data for an oral suspension. Some brands are film-coated and compounding instructions in some institutions suggest removal of this coating prior to preparing a suspension.
Shout out to “Pharmacy Tammy” for her anecdotal reports of nurses crushing hydroxychloroquine tablets at the bedside leading to clogged nasogastric tubes. If you have the resources to prepare this suspension for your nurses that sounds like the ideal scenario.
ISMP resource on common canister
Many hospitals are experiencing MDI shortage currently and/or are re-evaluating common canister policies in light of COVID-19. While they have not developed guidelines, the ISMP has an excellent article on this subject here.
When can evidence-based updates be expected?
Everyone is eagerly awaiting better evidence regarding therapeutics for the treatment of COVID-19. A reminder on some upcoming data that I discussed in episode 486:
Two randomized double blind placebo controlled trials of remdesivir are due to be complete in April. One is a study of 308 patients with mild/moderate disease and the other is a study of 453 patients with severe disease.
Several studies of hydroxychloroquine and chloroquine are underway and the earliest expected result is in May 2020. This does not include the trial reportedly being done in New York City of hydroxychloroquine and azithromycin.
To those APPE students whose hospital rotation has been disrupted by recent events: One way I’d like to help is by providing free access to 8 essential training videos on topics that I discuss with students on my rotation. Get free 14-day access by going to pharmacyjoe.com/virtual.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Dear Pharmacy Joe,
I just want to thank you again for your consistent dissemination of valuable information to us. I have been a fan of yours for many years now.
Thank you so much for your kind words!