Clinical trials of hydroxychloroquine for COVID-19 outpatients are safe

New research published in the preprint server medRxiv in July 2020 indicates that the use of hydroxychloroquine (HCQ) among outpatients in clinical trials, without high-risk factors for cardiac arrhythmia, is safe, with gastrointestinal side-effects being the most common and no fatal adverse outcomes.

The study focused on the safety evaluation of HCQ in outpatients, compiling data from three randomized controlled trials, where HCQ was used as pre-exposure prophylaxis, post-exposure prophylaxis, and early treatment, respectively. The researchers excluded all participants with contraindications to the use of this drug.

The study included approximately 2,800 individuals, with a median age of 40 years. About 60% of them were in good health. The researchers found that side effects were reported in around 85% of the participants, and 27% had one or more side effects related to the medication.

When the dosage frequency was compared, they found that about 30%, 35%, 30%, and 20% had side effects when the drug was administered daily, twice a week, once a week or when a placebo was used.

Around 30% of patients reported side effects in the trials where the drug was administered post-exposure or post-infection.

The most common side effects reported were gastrointestinal, namely, stomach upset or nausea, diarrhea, vomiting, or abdominal pain. Overall, these symptoms were reported in a quarter of patients on daily dosage (about 20% and 15% with twice-weekly or weekly dosage), and in 10% of those on placebo.

However, in the post-exposure placebo vs. treatment groups, the rate of gastrointestinal side effects was comparable. The side effects were rated as tolerable and not requiring the cessation of medication.

Other reported side effects included lightheadedness or dizziness and allergic reactions.

There were only two instances of cardiac arrhythmias in the whole patient population, one of which occurred in the placebo group, the other in a patient taking HCQ twice a week. There were no reported deaths in this low-risk population.

The study excluded hospitalized, presumably sicker, patients, who were mostly older. Most of the participants were health workers, and reasonably well-informed about health. Therefore, the safety of HCQ concerning its use in severely ill COVID-19 patients remains unclear.

Ongoing clinical trials are expected to safely continue with research participants and regulatory bodies reassured as to the general safety of hydroxychloroquine when using appropriate exclusion criteria.

The study is timely as new data shows the number of patients in the US who receive prescriptions for HCQ, chloroquine, and azithromycin has increased dramatically. Many patients are urging their doctors to write prescriptions for them, causing some pharmacies to run short on supply.

The market for HCQ is expected to grow at around 4% compound annual growth rate, between the years 2020 and 2030. Demand for the antimalarial has shot up following President Donald Trump’s promotion of the drug as potential treatment for coronavirus.

Manufacturers have rapidly invested in bolstering production capacities to keep up with the sudden, unprecedented demand.

In a letter published in JAMA Internal Medicine, corresponding author Daniel S. Budnitz, MD, MPH, of the Centers for Disease Control and Prevention, and colleagues used data from the IQVIA Total Patient Tracker to compare prescription rates between October 2019 and March 2020 at 48,900 retail pharmacies in the US.

The pharmacies dispensed an average of 383,685 prescriptions for HCQ per month, and 1839 prescriptions for chloroquine per month. However, from February to March, prescriptions for hydroxychloroquine jumped by 86.2%—from 367,346 to 683,999. Prescriptions for chloroquine jumped from 2346 to 6066—an increase of 158.6%.

Among those patients given hydroxychloroquine, the number who were simultaneously prescribed azithromycin jumped from 8,885 in February, to 101,681 in March—a 1044% increase.

The pandemic has highlighted the weaknesses in the drug supply chain, and increased trade tensions have further compounded the problems of bringing drugs to the US from parts of the world that commonly supply active ingredients.

The report showed significant variance from state to state when it came to prescribing trends. New Jersey, Florida, Hawaii, and New York reported the highest rates of increase. Each of those states saw prescriptions double. In the case of New Jersey, the rate nearly tripled.

States with the lowest increases were South Dakota and Iowa, which saw increases of less than 50%.

The data in the study do not include prescribing indications, so it’s not possible to know for sure the extent to which the increases in prescriptions are directly related to COVID-19.