The jury is still out on how much hydroxychloroquine and chloroquine actually help in the treatment or prevention of COVID-19, but desperate times have led desperate health care providers to use the antimalarial drugs to treat patients in desperate need of coronavirus cures.
The unintended consequence? The increased demand for the drugs has people with lupus and rheumatoid arthritis (RA) despairing over shortages of the drugs they have relied on for nearly 70 years.
Wednesday, the EMA reacted to the short supply by restricting the use of the two drugs to their authorized indications and to clinical trials or national use emergency programs for COVID-19.
“Chloroquine and hydroxychloroquine are vital medicines for patients with autoimmune conditions such as lupus. It is important that such patients are still able to obtain them and do not face shortages caused by stockpiling or use outside the authorized indications,” the EMA said.
The EU agency noted that some countries have already restricted the prescribing of the drugs to reduce the risk of shortages. Australia is one of those countries. Last week, the Therapeutic Goods Administration (TGA), in an effort to head off shortages, limited who could prescribe the drugs.
Under those restrictions, only certain types of specialists can prescribe hydroxychloroquine to new patients in Australia, the TGA said. General practitioners and other doctors can continue to prescribe hydroxychloroquine refills for registered indications for patients who had prescriptions prior to March 24, 2020.
In the U.S., it may be too late to avoid a shortage. Tuesday, the two drugs made their first appearance on the FDA’s drug shortage list since the COVID-19 emergency began. While the drugs are available, the supplies are limited. Manufacturers are increasing their production, but they’re warning of possible transportation issues.
Besides working with manufacturers to assess their supplies and to ensure production ramp-up occurs expeditiously and safely, the FDA is allowing outsourcing facilities to compound hydroxychloroquine. The agency also is evaluating the market demand for patients dependent on hydroxychloroquine and chloroquine for the treatment of malaria, lupus and RA.
A few days ago, Sandoz Inc. donated 30 million doses of hydroxychloroquine sulfate to the U.S. national stockpile, and Bayer AG donated 1 million doses of chloroquine phosphate to the U.S. Department of Health and Human Services for use in COVID-19 clinical trials and to treat patients hospitalized due to coronavirus infection.
The FDA said the donations should help ease the supply pressures for the drugs, adding that “this is a fluctuating and dynamic situation.”
The demand for the drugs has escalated over the last month, with orders for chloroquine spiking 3,000% in the U.S. in March, according to Premier Inc. As a result, the current fill rate for chloroquine orders is 19%. Orders for hydroxychloroquine jumped 260% last month; its current fill rate is 35%.
Increased demand due to COVID-19 also is threatening the supply of other drugs. According to a survey of Premier’s hospital members, antimalarial drugs were the most commonly reported shortage with 70% of hospital respondents reporting a shortage. That was followed by 65% reporting shortages of bronchodilators, 40% reporting antibiotic shortages, 38% indicating antiviral shortages and 35% noting a shortage of sedatives. Shortages are more prevalent in hot spots like New York, where 77% of hospitals with COVID-19 cases have reported shortages of antimalarials.
“Given that hospitals are on the front lines of COVID-19 treatment, they are experiencing the shortages first and more acutely than other providers,” Premier President Michael Alkire said. He stressed the need for a dynamic allocation process that matches available supply to the areas with greatest need, while balancing the COVID-19 surge demand in hospitals with the ongoing demand from patients who use the drugs for chronic conditions.
Meanwhile, more and more trials are underway across the globe to test hydroxychloroquine and chloroquine against COVID-19, increasing the demand for the drugs. The University of Washington is taking the lead in one of the newest trials – a multisite study aimed at determining whether hydroxychloroquine can prevent transmission in people exposed to the virus. The randomized, placebo-controlled trial will enroll 2,000 doctor-referred participants who are close contacts of people with a confirmed or pending COVID-19 diagnosis.
Participants will be randomly assigned to take hydroxychloroquine, donated by Sandoz, or a placebo over two weeks. Daily self-collected nasal swab samples will be tested to confirm new COVID-19 infections across the two groups. The eight-week trial should provide answers within a few months. Data from the trial will be shared via the open-access COVID-19 Therapeutics Accelerator website, according to the university.
Another trial testing hydroxychloroquine’s ability to prevent COVID-19 transmission got the go-ahead Wednesday from the Patient-Centered Outcomes Research Institute (PCORI). The institute approved up to $50 million to fund a trial testing the drug in U.S. health care workers who are exposed to the virus and to create a registry of health care workers interested in participating in future research.
Led by the Duke Clinical Research Institute, the trial is to begin enrolling about 15,000 registry participants later this month. They will receive either hydroxychloroquine or a placebo for 30 days and then be followed for two months. In addition to prevention, the trial will assess whether the drug can hold down the amount of virus asymptomatic health care workers might unintentionally spread to others.