Search for COVID Treatments

In the ongoing battle against COVID-19, President Trump continues to encourage the use of hydroxychloroquine (HCQ) and chloroquine (CQ) as a potential treatment for the virus before ongoing studies have been able to confirm its efficacy and safety.

While research continues to study the potential of this medication, it’s critical to know that using this drug in combination with other routine medications could be fatal.

A study published on April 4, 2020, by the Preprint Server for Biology: BioRxiv reports that combining HCQ or CQ with metformin killed 30 to 40 percent of mice, proving it to be a highly toxic combination.

“We observed that the combination of CQ or HCQ and metformin, which were used in our studies as potential anti-cancer drugs, killed 30-40% of mice,” explains the study which used a method called “allometric scaling” to ensure the dose given to a mouse is comparable to the dose a human would take.

“While our observations in mice may not translate to toxicity in humans, the reports that CQ or HCQ has anti-COVID-19 activity, the use of CQ resulting in toxicity and at least one death, and the recent Emergency Use Authorization (EUA) for CQ and HCQ by the US Food and Drug Administration (FDA) prompted our report.”

Considering metformin is one of the most widely prescribed drugs across the globe as the “first line of defense” in treating type 2 diabetes, it’s critical for patients to know they should not acquire and begin taking HCQ or CQ on their own.

Let’s take a closer look at HCQ and CQ.

What are hydroxychloroquine (HCQ) and chloroquine (CQ)?

Initially created to treat malaria and autoimmune diseases like lupus and rheumatoid arthritis, HCQ and CQ have also been evaluated closely in ongoing research as potential treatments for some types of tumor-based cancers.

In the drug class “antimalarials”, HCQ and CQ are powerful drugs that should not be taken without careful observation and management through your healthcare team.

Metformin and HCQ are not the only concerning drug combinations. Other precautions to consider before taking HCQ or CQ include:

• if you are allergic to hydroxychloroquine, chloroquine (Aralen), primaquine, or any other drugs
• if you are taking other prescription and nonprescription drugs, especially acetaminophen (Tylenol, others), digoxin (Lanoxin), iron-containing medications (including multivitamins), isoniazid (Nydrazid), methotrexate (Rheumatrex), niacin, rifampin (Rifadin, Rimactane), and some vitamins or herbal products
• if you have or have ever had liver disease, psoriasis, porphyria or other blood disorders, G-6-PD deficiency, dermatitis (skin inflammations)
• if you drink large amounts of alcohol
• if you have ever had vision changes while taking hydroxychloroquine, chloroquine (Aralen), or primaquine
• if you are pregnant, plan to become pregnant, or are breast-feeding 
• If you become pregnant while taking hydroxychloroquine, call your doctor
• US cardiologists have also warned that HCQ and CQ can cause abnormal heart rhythms

Mild side-effects of HCQ and CQ can include:

• headache
• dizziness
• loss of appetite
• nausea
• diarrhea
• stomach pain
• vomiting
• skin rash

More severe side-effects can include:

• reading or seeing difficulties (words, letters, or parts of objects missing)
• sensitivity to light
• blurred distance vision
• seeing light flashes or streaks
• difficulty hearing
• ringing in ears
• muscle weakness
• bleeding or bruising of the skin
• bleaching or loss of hair
• mood or mental changes
• irregular heartbeat
• drowsiness
• convulsions

If you are taking this drug, you should report any of these side-effects to your healthcare team.

Why is the combination of HCQ and metformin potentially fatal?

Contrasting Mechanisms

HCQ and CQ significantly impact a natural bodily process known as “autophagy” which essentially means the degradation and recycling of damaged cells.

In the treatment of cancerous tumors, this is likely a helpful thing, explains researchers from BioRxiv.

“Autophagy literally stands for “self-eating” and is a form of ‘quality control’ that most cells in our body engage in to recycle aging proteins, so as to synthesize new ones. HCQ and CQ are both agents that inhibit autophagy and in fact, this is the property that is important for its use in tumors like pancreatic cancer.”

In contrast, metformin actually induces autophagy, which leads researchers to believe that these two drugs are crossing paths in a way that causes the accumulation of “autophagosomes.”

Autophagosomes are “essentially recycling bins, containing cell proteins to re-purposed.”

In the mice that died after taking both HCQ and metformin, there was an increased amount of autophagosomes in the heart, liver, and kidneys. 

Contrary Study

A small 2014 study featuring 267 participants in India concluded the opposite — stating that the treatment was well-tolerated by patients with type 2 diabetes also taking metformin.

Healthy Patient Usage

There have been several deaths since the president first began recommending the drug which should tell everyone that HCQ and CQ should only be taken under careful supervision of your healthcare team after carefully evaluating your overall health.

“There are very good safety data on both drugs individually, as well as safety data on this combination being used in patients who have autoimmune diseases like lupus and rheumatoid arthritis. However, patients with COVID-19 are a whole different ball game and typically much sicker than the average population,” explains authors of the 2020 study.

High-Risk Patient Usage

“We have to remember that COVID-19 has been associated with adverse effects on the heart and the blood vessels – how all of these play out, in addition to the two drugs interacting with each other will need to be studied.”

The CDC continues to emphasize that those at the highest risk of dying due to COVID-19 are people with other underlying health conditions — including diabetes.

The results are neat and demonstrated the toxicity of this drug combination,” said Gaetan Burgio, MD, PhD, an infectious diseases expert from the Australian National University.

Burgio thinks the results in mice are highly likely to mimic the results in humans.

“Metformin is a common anti-diabetic which millions of people are taking. HCQ/CQ can give cardiac toxicity and are not innocuous. Regardless of the treatment combination, HCQ/CQ treatment might lead to more risks than benefits. I would urge anyone to consult with a doctor before initiating such treatment,” added Burgio.

Tracking Each HCQ/CQ Patient

To move forward safely, the researchers explain the need for a thorough registry of every COVID-19 patient that is taking HCQ or CQ in order to fully understand its potential and safety.

“This will allow us to sift through potential adverse drug interactions like metformin and others.”

Until then, we should not begin taking this off-label on our own to prevent or treat COVID-19. Only through careful medical guidance and supervision should HCQ or CQ be taken, especially by those taking other medications like metformin.