Medication Spotlight: Hydroxychloroquine

Author: Chris Verdi, PharmD, President, Parafill

There are few medications more widely discussed and more controversial these days than the prospective COVID-19 treatment Hydroxychloroquine (HCQ). For this reason I was hesitant to make this month’s Medication Spotlight post about this drug. It seems that the mere mention of it produces anxiety in patients and providers alike. However, for that same reason, I thought it necessary to discuss here. So let’s take a basic look at HCQ, common side effects or toxicities of the medication, and its potential utility (or lack thereof) in treating COVID-19.

Who takes it and how does it work?

Before the COVID-19 pandemic, HCQ was a daily medication for many patients suffering from lupus, rheumatoid arthritis, and part of a treatment course for malaria. It is a common prescription, one that has found itself on the top 100 most prescribed medications list every year for decades. In fact, it was first approved by the FDA in 1955, when Dwight Eisenhower was president. That is to say, HCQ is a well known medication to just about every doctor and pharmacist. 

Discussing how it works in the body is where it gets a little bit complicated. Actually, it’s not even entirely understood. What we do know about the medicine is that it is a “weak base”, meaning that it has a high pH, or is the opposite of an acid. It is thought to work by changing the pH at targeted sites within the body. This sounds minimal, but changing pH is a big deal. Minor changes in pH at targeted sites around the body can have significant impacts. All of the proteins in our body (and in the “bodies” of parasites, or perhaps viruses) function within a very delicate pH range, and subtle changes can be harmful or even lethal. 

So how does this weak base work to treat patients?  In the treatment of malaria, it is proposed that HCQ changes the pH in a particular site in the parasite (Plasmodium), inhibiting its “digestive” functions, and causing it to die off. In lupus and rheumatoid arthritis patients, the alteration of cellular microenvironment pH is thought to inhibit the movement of inflammatory mediators in their bodies, and thus reduce the symptoms associated with these conditions. In the case of COVID-19, it is thought that the change in pH on the surface of our cells will prevent the virus from being able to attach itself to and enter our cells. 

Does it work in treating COVID-19?

Here is where we open the can of worms. It is early days for having a definite answer to this question, but I’ll give it a try. There were some early French and Chinese trials that suggested a possible benefit of using HCQ to treat COVID-19. I have to be clear, these trials did not meet any traditional threshold for the level of evidence required to establish safe and effective treatment of a disease. But nonetheless, HCQ has made its way into many COVID-19 treatment regimens around the country. The trial use of HCQ in hospitals without a great deal of evidence is due to the challenges related to dealing with a novel virus that has gone pandemic. We simply don’t have the benefit of years of clinical data that typically accompany the decision to prescribe a treatment.

The evidence that HCQ can successfully treat the coronavirus at this point is mixed. The early “trials” that led to its use in hospital algorithms have come under some serious scrutiny recently. Particularly those of the French physician-researcher Didier Raoult, which involve the use of HCQ in combination with an antibiotic Azithromycin (yes, the drug from the z-pak). More recent trials, however, have brought the effectiveness of HCQ in treating coronavirus under question. A Brazilian trial of chloroquine (a sort of “sister” drug to HCQ) had to be stopped because of limited evidence of benefit and significant drug side effects. Another recent review of clinical data published on April 10th showed no benefit for use of HCQ in COVID-19 positive patients that required supplemental oxygen. This study also showed that HCQ caused serious side effects.

At this point there is only one certain conclusion. While we may find over time with larger studies that there is some benefit in treating COVID-19 with HCQ, there is only one thing that is certain now: HCQ is no magic bullet that will take down the coronavirus. 

But if it might work for COVID-19, why not try it?

It seems logical enough that if there may be some evidence that HCQ could treat COVID-19, why not give it to everyone who is diagnosed? The first reason is that the risks of serious side effects with HCQ do not make a compelling argument from a benefit-harm perspective. The main risk is cardiac toxicity. The use of HCQ, particularly alongside Azithromycin, can cause a dangerous and life-threatening cardiac arrhythmia called torsades de pointes. Your normal heart rhythm should look something like this:

In a patient with torsades de pointes, it looks more like this:

This heart rhythm makes it difficult for your heart to effectively do its job. Medications that have a risk of increasing risk for torsades are always closely monitored, particularly when multiple are given at the same time – like with HCQ and azithromycin. 

Beyond the benefit-harm analysis, we must consider those who need HCQ for their chronic conditions. The recent run on HCQ has left the supply chain diminished for those who need treatment for lupus or rheumatoid arthritis. Within days of the early reports that HCQ was being used for COVID-19 treatment, wholesalers around the country were entirely out of stock on this necessary daily medication for many patients across the country. 

Conclusion

The beauty of the scientific process is that we will have clear answers to all of these questions in the future. So many promising medications are being studied right now for those who are ill. Social distancing is going a long way in preventing the rapid growth in the number of new patients (I’m proud of my state of Ohio and how well we have done!). The best treatment remains prevention. 

I hope this information has proven helpful. We will get through this pandemic together. If you have any questions or comments, want to share your thoughts, reach out! You can get ahold of me here:

Email: chris@parafill.com Twitter: @ParafillCEO

In health,

Chris 

Keywords:

Coronavirus, Hydroxychloroquine, Chloroquine, Azithromycin, Didier Raoult, SARS-CoV-2, Rheumatoid Arthritis, Lupus, Malaria, Plasmodium