Episode 486: Medications that have in vitro but otherwise unproven activity against COVID-19

In this episode, I’ll discuss medications that have in vitro but otherwise unproven activity against COVID-19.

Do you want Monday’s podcast episode to be about meds that have in vitro but otherwise unproven activity against COVID-19 or some other topic that has nothing to do with COVID-19?

— Pharmacy Joe (@PharmacyJoe) March 14, 2020

At the time of this writing, there are no treatments for COVID-19 that have in vivo clinical data supporting their use. Any available data is limited to case reports and in vitro studies. This information is provided not to recommend a course of treatment for patients with COVID-19; it is to list the medications with in vitro but otherwise unproven activity against the virus and when applicable provide information on when in vivo clinical data is expected to become available.

Should specific treatments become recommended for COVID-19, spaces to watch for information include:

CDC resources , IDSA resources , and WHO resources.

Remdesivir

Perhaps the most promising treatment is the broad-spectrum anti-viral medication remdesivir. This is a nucleotide analog that inhibits RNA synthesis. The COVID-19 virus belongs to the betacoronavirus family, in which the SARS and MERS viruses also belong. Remdesivir has shown in vitro activity against the SARS and MERS viruses, as well as several other coronaviruses. In a letter to the editor in the journal Cell Research,  a study of 7 different medications in vitro is described where remdesivir potently blocked virus infection at a low-micromolar concentration.

There are clinical trials of remdesivir currently underway to evaluate its use in patients with COVID-19. Two of these trials are taking place in China with study medication provided by the manufacturer Gilead. Both trials are expected to be completed in April of 2020. One is a study of 308 patients with mild/moderate disease and the other is a study of 453 patients with severe disease. These are randomized, double-blind, placebo-controlled trials.

Gilead, the manufacturer of remdesivir, is also beginning randomized open-label trials in patients with COVID-19 this month. In addition, the NIH has begun an adaptive, randomized, double-blind, placebo-controlled trial into remdesivir as a potential treatment for hospitalized adult patients diagnosed with COVID-19.  Although the clinical trials database states results for this trial are not expected until 2023, that is likely referring to the end of the adaptive design; results specifically on remdesivir may be available much sooner.

Gilead states they have a stockpile of the medication that they are using for compassionate use requests and are increasing the manufacturing of the medication prior to knowing for certain if it is effective. Compassionate use requests must be initiated by the patient’s treating physician. Instructions and an email to start this process are located on this page.

Chloroquine & hydroxychloroquine

The same letter to the editor that claimed in vitro activity of remdesivir against COVID-19 said that chloroquine had a similar effect. A study since published in Clinical Infectious Diseases found in vitro that hydroxychloroquine reached 3 times the potency of chloroquine to inhibit COVID-19. The authors stated:

Based on physiologically-based pharmacokinetic models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

 

As the listener “Pharmacy Hanan” commented on episode 484, there is a theory that the addition of zinc 500 mg po twice daily (Dose is not provided in South Korea COVID-19 treatment guidelines – thank you Pharmacy Jay!) will enhance the effects of chloroquine and hydroxychloroquine.   Several studies are underway evaluating this but the earliest expected result is in May 2020.  These studies can be found here, here, and here.

Lopinavir/ritonavir

The combination lopinavir/ritonavir was helpful in the treatment of SARS and is therefore hoped to be of use against COVID-19.  There is a published case report where starting lopinavir/ritonavir coincided with COVID-19 viral load decrease. Several trials are underway with the earliest results expected in May 2020.

Ribavirin and sofosbuvir

The anti-hepatitis C medications ribavirin and sofosbuvir appeared in an in vitro study of RNA polymerase to inhibit COVID-19.  Only ribavirin has a study underway given in combination with lopinavir-ritonavir and beta-interferon but results are not expected until July 2022.

Interferon beta

Interferon beta has been shown to protect mice from the MERS virus and it is hoped based on this data it may have a similar effect in humans with COVID-19.  The proposed mechanism of action is by preventing entry of the virus into cells.

Tocilizumab

The IL-6 inhibitor for rheumatoid arthritis tocilizumab has reportedly been used empirically in some severe COVID-19 cases in China based on the data that critically ill COVID-19 patients had elevated IL-6 levels.

If you have knowledge of another medication that belongs on this list please reach out to me at joe@pharmacyjoe.com.

---

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.

---

<– Previous Post                    Next Post –>