What do you tell patients?
First, the evidence for the medications benefit in COVID-19 remains thin, at best. One study showed that the quinine derivatives inhibited coronavirus strains in vitro. One small, open-label, nonrandomized study in humans, conducted in France, showed promising results for hydroxychloroquine in patients with the novel coronavirus, and even better results when the drug was combined with azithromycin. Another small study from China found no benefit from hydroxychloroquine in COVID-19.
While the studies provide some hope, patients should be cautioned that many drugs that perform well in in vitro studies fail to demonstrate the same effect when tested in humans. The French study has also drawn considerable criticism for its methodology. Virtually all scientists agree that larger, more rigorous clinical trials are needed.
Beyond that, the drugs have some significant side effects, even with short-term use, that may be especially risky in the setting of COVID-19. A review published in the Canadian Medical Journal last week by David Juurlink, MD, of the Sunnybrook Hospital in Toronto, highlighted some of the most notable risks associated with using the malaria drugs for a novel coronavirus infection.
Both Chloroquine and hydroxychloroquine can prolong the QTc interval, a risk increased in patients with pre-existing cardiovascular disease. A longer QTc interval is associated with cardia arrhythmias and sudden cardiac death. The potential adverse effect on the heart is especially troubling given recent reports indicating that more than 20% of COVID-19 patients suffer heart damage from the disease. Combining the drugs with azithromycin could increase their danger, as the FDA has warned that the antibiotic may increase the risk of fatal heart rhythms, particularly in patients with QT-interval prolongation.
Chloroquine and hydroxychloroquine also increase the risk of hypoglycemia, Dr. Juurlink said. Multiple studies have found that individuals with diabetes have a greater risk of suffering more severe coronavirus infection and dying from the disease. Older people also face greater risk from COVID-19. For diabetic or older patients, and especially older patients with diabetes, hypoglycemia could pose significant danger of falls, loss of consciousness, and death, particularly outside of a hospital.
Patients taking the malaria drugs sometimes experience neuropsychiatric effects, including agitation, confusion, hallucinations, and paranoia, the review noted. As hypoxia, a common symptom in patients with more serious cases of COVID-19, also causes mental confusion, and about half of elderly hospitalized patients experience delirium, the total impact on an elderly person’s cognitive function and mental state could be devastating.
Individuals may metabolize the drugs very differently and the drugs interact with a large number of other medications, making knowing the right dose for each patient quite challenging. Getting it wrong could have serious consequences, too, as chloroquine and hydroxychloroquine are both highly toxic in higher doses. Overdoses can cause seizures, coma, and cardiac arrest, according to Dr. Juurlink.
"Despite optimism (in some, even enthusiasm) for the potential of chloroquine or hydroxychloroquine in the treatment of COVID-19, little consideration has been given to the possibility that the drugs might negatively influence the course of disease," Dr. Juurlink said. "This is why we need a better evidence base before routinely using these drugs to treat patients with COVID-19."
