FDA: Benefits of HCQ or CQ Do Not Outweigh Risks for COVID-19

By Marie Rosenthal

Saying the benefits no longer outweigh the potential risks, the FDA revoked the emergency use authorization (EUA) for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) to treat COVID-19.

The EUA allowed hydroxychloroquine and chloroquine to be donated to the Strategic National Stockpile to be used to treat certain hospitalized patients with COVID-19 when a clinical trial was unavailable, or participation in a clinical trial was not feasible. The agency determined that the legal criteria for issuing an EUA are no longer met.

“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency said in a statement.

“It was not surprising to see the announcement,” said Michael Ganio, PharmD, MS, BCPS, FASHP, the director of pharmacy practice and quality at ASHP.

“There's been mounting evidence that the drug is not effective in treating hospitalized COVID-19 patients. At some point, the amount of evidence about the lack of benefit outweighs the risk of treating patients with hydroxychloroquine or chloroquine.”

In April, just four weeks after granting the EUA, the FDA issued a warning about reports of serious arrhythmias in patients with COVID-19 treated with either drug, especially when prescribed with azithromycin and other QT interval?prolonging medicines. The warning reminded physicians that the EUA was not a new drug approval, but allowed the drug to be used in clinical trials: “We are also aware of increased use of these medicines through outpatient prescriptions. Therefore, we would like to remind health care professionals and patients of the known risks associated with both hydroxychloroquine and chloroquine,” the agency said in a statement at the time, adding it would continue to investigate the reports, which included arrhythmias, such as QT interval prolongation and ventricular tachycardia.

As of May 6this year, 347 HCQ and 38 CQ cases with possible adverse events (AEs) were identified, according to the FDA. Most of the cases occurred among men in their early 60s. Five cases reported HCQ use through the EUA. The most commonly reported AE was QT interval prolongation for both HCQ and CQ, according to the FDA.

There were 109 cases with serious cardiac AEs, some reporting one or more of the following:

80 reported QT prolongation;
four reported torsades de pointes;
14 reported ventricular arrhythmia, ventricular tachycardia or ventricular fibrillation; and
25 had a fatal outcome.

Among the 109 cases, 92 (84%) reported concomitant use of at least one other medication that prolongs the QT interval and 75 (69%) reported concomitant use of azithromycin.

There were 113 cases with serious noncardiac AEs, and among those, hepatitis, increased liver enzymes and hyperbilirubinemia were the most common conditions.

In addition to the AEs reported, the FDA said it considered many factors before rescinding the EUA, including an announcement by the chief investigators of the RECOVERY trial, which closed the hydroxychloroquine arm of its study on June 5, due to a lack of benefit.

Sponsored by Oxford University in the United Kingdom, the RECOVERY trial is assessing the effectiveness of different potential COVID-19 treatments in their ability to reduce all-cause mortality within 28 days. More than 11,000 patients have been enrolled so far. The study randomized 1,542 patients to HCQ and 3,231 to the usual care comparator, and an interim analysis found that mortality trends favored usual care. In the HCQ arm, mortality was 25.7% and in the usual care arm was 23.5% (hazard ratio, 1.11; 95% CI, 0.98-1.26).

The agency said there are still several studies examining the use of HCQ or CQ in COVID-19.

By itself, Dr. Ganio said rescinding the EUA would not stop any of the trials; however, institutional review boards overseeing those trials might request preliminary data to decide whether they should be continued.

The agency also cited the guidelines of the Infectious Diseases Society of America, which said there were no good clinical data to recommend HCQ or CQ. “The Infectious Diseases Society of America supports the decision of the FDA to revoke emergency use authorization for hydroxychloroquine and chloroquine as studies so far have not shown these medications to be effective for treatment of COVID-19,” said IDSA President Thomas M. File Jr., MD, FIDSA. He said the IDSA would update its guidelines to reflect the new data that have been emerging.

One adverse event that might be rectified by this announcement is shortages of these medications. In addition to malaria prophylaxis, they are used to treat certain patients with rheumatoid arthritis and lupus. These patients have been having trouble filling their prescriptions. Dr. Ganio said he hoped fewer outpatient prescriptions would be written for people trying to use the drugs as prophylaxis, thus increasing the number of arthritis and lupus patients who can regain access to the medications.

Dr. Ganio said pharmacists are going to be asked about the medications and they need to have a discussion about the risks and benefits, especially for people who want to use the medications prophylactically. Pharmacists should consider the patient’s medical history, what medications they might be taking and their risk for infection with COVID-19, he said.

“As our body of knowledge expands in response to the COVID-19 pandemic, our nation must remain committed to following the science and ensuring policies that protect the health of residents as we investigate effective treatments to counter this insidious virus,” Dr. File said in a statement.

Covid-19

FDA: Benefits of HCQ or CQ Do Not Outweigh Risks for COVID-19

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