THE TRUTH ABOUT HYDROXYCHLOROQUINE (Plaquenil) IN THE TREATMENT OF COVID-19
By Dr. Alain Mass
Since the intervention of the President of the USA, Donald Trump announcing that the FDA approved Hydroxychloroquine in the treatment of COVID-19, the news spread that a treatment was now available. However, on the same day, the FDA denied having given the approval for this drug. We are now facing questions and requests from patients for this medication that medical professionals cannot give without going astray from the current standard of care established by the FDA. More concerning is the consequences on the epidemic and on lives to refrain the prescription of Hydroxychloroquine. Is Hydroxychloroqine really a treatment for COVID-19? Is there any alternative treatment? Is Hydroxychloroquine really dangerous to the point to limit or to delay its use until studies confirm the validity of its use in the treatment of COVID?
Didier Raoult, M.D. is a Professor in Infectious Diseases in Marseille, France. He is ranked as the first world expert in communicable diseases by the online resource, http://www.expertscape.com. He is the leader in France in the research on COVID-19. He is also an expert in Plaquenil since he has worked for the past 10 years on Plaquenil to treat other diseases. He is currently the European voice who promotes the use of Hydroxychloroquine against the position of the FDA. As a French native, I was able to follow the interviews that the Professor Didier Raoult gave and because lives may be saved today with the use of Hydroxychloroquine I feel an ethical duty to share the expert advice that supports the use of Hydroxychloroquine (Plaquenil).
Plaquenil has been used for the past 70 years as a drug to treat and to prevent malaria. Plaquenil’s safety has been proven, having been used by millions of people during this period. Its safety profile is well-known, which is not the case of newer drugs that may be safe in the early studies, but often turn out to be dangerous over time.
If, two months ago, you would have to go to Africa, Asia or any endemic zone of malaria the same doctor who, today, refuses to give you Plaquenil, based on the FDA instructions, would have given you Plaquenil for weeks or months without any hesitancy and probably even without looking up the potential side effects. Malaria may kill and the prevention of a potential lethal disease has justified for the past 70 years this practice that nobody never discussed. Suddenly, in 2020, Plaquenil became a dangerous drug when there is a threat of crisis in Plaquenil supply. Is Malaria much worse than COVID-19? Is the risk of being bitten by a mosquito in a hotel much higher than catching COVID-19 in your local supermarket full of sick individuals or by touching door knobs where the virus can stay 9 days?
Three studies have been published recently by Chinese doctors showing the efficacy of Plaquenil on COVID-19. One study reported by the Pr. Didier Raoult, showed the eradication of coronavirus in 75% of patients with hydroxychloroquine alone and when combined with Azithromycin an eradication in 95% of cases. Pr. Raoult published a few days ago his own study showing similar results. Pr. Raoult thinks that Chinese doctors are reliable. They were the first to face this epidemic, have the largest experience in COVID-19 patients and have already published more than 20 studies.
The usual rule in Medicine requires protocols, well conducted double-blind randomized studies, studies at large scale to officially promote a medication. Dr. Hahn, director of the FDA states:
“We must ensure these products are effective: otherwise we risk treating patients with a product that might not work when they could have pursued other more appropriate treatments”.
The problem is that we do not have yet these “more appropriate treatments” and people in ICU cannot wait.
Today, there is no other FDA approved drug to fight against COVID-19. Today, while people may be between life and death, when some do not know how fast and severely they will deteriorate, Plaquenil, which is FDA approved for the treatment and prevention of malaria and for some inflammatory diseases, is still not approved for the treatment of COVID. The FDA ensures the safety and the good use of medications and physicians who today refuse to give Plaquenil, strictly, follow the FDA instructions in your best interest. Is it really so?
The history of Medicine can also teach us lessons. One oral antidiabetic medication (Metformin) was introduced in Europe in 1950 and in the USA in 1995. It took 45 years for the FDA to authorize what turned out to be the basic treatment of diabetes. The first oral anti-diabetes medication was introduced in the USA in 1984. It took 14 years for the FDA to allow american citizens to have tablets instead of insulin shots. It took 12 years for Alexander Fleming to convince his peers that penicillin was not a quackery resulting in the death of hundreds that was avoidable. How many victims from COVID-19 will it take until pragmatic therapeutic approaches are taken? The concept of the patient’s best interest has to be reconsidered in times of crisis. Yes, well-conducted studies are necessary and should guide our medical practice. Sometimes, however, when it is urgent, the risk/benefit ratio may be the only guide.
The common Plaquenil side effects may include nausea, vomiting, stomach pain or cramps, loss of appetite, weight loss, diarrhea, dizziness, spinning sensation, headache, ringing in your ears, mood changes, nervousness, irritability, skin rash, itching, or hair loss. As to the serious side effects, their frequency according to the medical website Medscape is not well defined. Plaquenil may also cause severe eye damage but only when taken for a long term. This concern is certainly not relevant to a 5 day treatment. Plaquenil may have an effect on the heart visible on an electrocardiogram (EKG) (prolongation of the QT interval) as does Zithromax. The concern is the risk of cardiac arrhythmia. The risk is even greater when Plaquenil is combined with other drugs that also prolong the QT interval on EKG. A study in 2018 concluded that more studies are needed to evaluate the clinical significance of this EKG abnormality. Pr. Didier Raoult who has used Plaquenil for the past 10 years in his clinical practice and research writes that the combination of Hydroxychloroquine (Plaquenil) with Azithromycin (Zithromax) was a concern but has not yet been shown to cause EKG problems. An EKG is advisable before starting Plaquenil. Any prolongation of the QT interval requires the approval of a cardiologist to use Plaquenil. In his interview on 03/23/20, the Pr. Raoult speaks of an hypothetical but possible risk of arrhythmia that is more relevant to patients who present with multiple diseases or in the ICU setting.
Drug interaction: Plaquenil may interact with acetaminophen, cancer medications, tuberculosis medications, birth control pills or hormone replacement therapy, arthritis medications, ACE inhibitors, antibiotics, antifungals, cholesterol medications, HIV/AIDS medications, NSAIDs (non-steroidal anti-inflammatory drugs), or seizure medications.
Side effects must always be correlated with their frequency, and with the risk/benefit ratio. Any medication may have serious side effects. Pr. Raoult, expert in the use of Plaquenil in his interview on 03/23/20 seems to be very annoyed by the warning about side effects and goes up to stating that it is purposely done like to “frighten people with ghosts”. Again, He insists on the fact that several millions of individuals took Hydroxychloroquine over the past 70 years. He does not hesitate to say that the fear of side effects due to Hydroxychloroquine and Azithromycin (Zithromax) does not make sense.
The risks of COVID-19 in a selected population at risk are serious and potentially lethal. In people at high risk of dying from COVID-19, the risk/benefit ratio favors the use of Plaquenil. Pr. Raoult, in his interview on 03/23/20 states that when there is respiratory insufficiency the virus is almost not or no longer detectable. When patients start having severe respiratory insufficiency, when patients are admitted in ICU, it is just too late to initiate Plaquenil. The virus is already gone. It is the remaining inflammation (cytokine storm) that is a life threat. According to the Pr. Raoult Hydroxychloroquine should be initiated when COVID-19 becomes moderate or when patients start getting worse. Plaquenil should be used when the virus is multiplying not when it is almost or totally gone.
Focusing on serious side effects without considering their relative frequency of occurrence and without taking into consideration the immediate life-threatening status and the absence of other alternative therapy causes an unrealistic and unjustified threat and fear on a medication that has the ability to save lives.
I understand that the authorization to use Plaquenil in the treatment of COVID-19 may lead to unjustified use of this drug where the risk/benefit ratio would not favor the drug, a shortage of this medication and the impossibility to give to those who really need it, for COVID-19 or for other indications. Providers should determine based on their clinical judgment and ethics what to do. However, today people are in ICU, others will have to be admitted in ICUs. These people cannot wait for studies to be completed.
Alain Mass, M.D.
Board Certified in Family Practice
Coronavirus and Plaquenil in the medical literature