Hydroxychloroquine use may lead to irregular heartbeats, low blood sugar

The drugs chloroquine, hydroxychloroquine and azithromycin, being used to treat and prevent COVID-19 despite weak evidence for their effectiveness, may have adverse side effects on patients like irregular heartbeats and reduced blood glucose levels, a new study says.

The review research, published in the Canadian Medical Association Journal, provides an overview of potential harms associated with these drugs as well as their management based on the best available evidence. 

 Physician and patients should be aware of several rare but potentially life-threatening adverse effects of chloroquine and hydroxychloroquine," said David Juurlink, Division of Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, and a senior scientist at ICES.

According to the scientists, the potential adverse effects of these drugs include irregular heartbeats, reduced blood glucose levels, neuropsychiatric effects, such as agitation, confusion, hallucinations, and paranoia.

They said some people's bodies process chloroquine and hydroxychloroquine poorly, and a small percentage metabolise them rapidly, affecting their response to treatment.

Chloroquine and hydroxychloroquine, the scientists said, are highly toxic in overdose and can cause seizures, coma, and cardiac arrest.

 The researchers added that indescriminate use of hydroxychloroquine may make it unavailable to patients with autoimmune disorders -- such as rheumatoid arthritis, lupus, and other chronic diseases -- who are mainly prescribed the drug. 

According to the review, the evidence that these treatments might be beneficial in patients with COVID-19 is of poor quality,  and it is possible that the drugs could worsen the disease. 

"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," said Juurlink. 

"This is why we need a better evidence base before routinely using these drugs to treat patients with COVID-19," he added.

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Azithromycin Reduced Treatment Failure in Severe, Acute COPD Exacerbations

The antibiotic azithromycin may reduce treatment failure in patients hospitalized for an acute exacerbation of COPD, according to a randomized, controlled trial published online in the American Journal of Respiratory and Critical Care Medicine.

Researchers in Belgium report that adding a low dose of azithromycin to the medicines prescribed while in the hospital and continuing a low dose of the antibiotic for three months after hospitalization reduced treatment failure compared to standard of care alone.

The researchers defined treatment failure as the need to intensify treatment with systemic corticosteroids and/or antibiotics, transfer the patient to the intensive care unit or readmit the patient to the hospital after discharge, and death from any cause.

Previous studies have shown that azithromycin prevents acute COPD exacerbations, but whether the antibiotic could reduce the need to intensify care of patients hospitalized for an exacerbation or improve their chances of not having another exacerbation once they left the hospital was unclear.

“We wanted to establish a new treatment option for acute exacerbations with hospitalization as current treatments are clearly insufficient,” said Wim Jannssens, MD, PhD, senior study author, professor of medicine at KU Leuven and a pulmonologist at University Hospitals Leuven. “Equally important, we wanted to see whether continuing azithromycin for a relatively short time after leaving the hospital could interrupt the vicious cycle of relapse, even after treatment withdrawal.”

The study enrolled 301 patients at 20 Belgian hospitals. Half the patients were given azithromycin, the other half a placebo, in addition to the medicines their physicians would normally prescribe to resolve the exacerbation.

Patients in the azithromycin arm of the study received 500 mg/day for three days while hospitalized, and then received 250 mg twice weekly for three months once they left the hospital. The study found that the rates of treatment failure were 49% for those in the azithromycin group vs 60% in the placebo arm.

Those receiving the antibiotic spent 24% fewer days in the hospital and 74% fewer days in the ICU than those taking the placebo. Mortality among those in the azithromycin group was half of the placebo group: 2% vs 4%.

These benefits appeared more pronounced among non-smokers. Current smokers experienced little or no benefit from low-dose azithromycin.

The researchers also studied the effects of withdrawing azithromycin at the end of three months and found that six months later the clinical benefits of the antibiotic were lost.

However, the study did not reach its goal of 500 participants and researchers said the “underpowered” study did not demonstrate statistical significance of time to treatment failure.

Although the study could not prove statistical significance of its primary endpoint, “a positive message of the trial is that our strategy reduced hospital time, days in the ICU and recurrent exacerbations in the most severe COPD group,” Janssens said, adding that a large phase 4 study with hospital readmission as the primary endpoint would be necessary before broad implementation of the current study’s findings.

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