The U.S. has all but exhausted its supplies of two anti-malarial drugs that are being used by some doctors in the U.S. and China to treat the coronavirus, but which lack definitive evidence as effective treatment or approval from the Food and Drug Administration.
The sudden shortages of the two drugs could come at a serious cost for lupus and rheumatoid arthritis patients who depend on them to alleviate symptoms of inflammation, including preventing organ damage in lupus patients.
Several new studies have shown the possible benefits of hydroxychloroquine and chloroquine, but medical experts are cautioning there is no solid evidence they have any effect on coronavirus. At Trump’s behest, the FDA is considering launching a broad clinical study to document whether they really work.
Even with the deep uncertainties, some doctors have been prescribing the drug as a preventive measure as well as a treatment. The phenomenon, known as “off-label'' prescribing, has depleted already limited supplies.
“It’s gone. It’s not in the pharmacy now,'' said Alexander Morden, a physician in Queens who is taking the drug in the hope of staving off infection. He said he has prescribed hydroxychloroquine to about 30 of his patients as a prophylactic and as a treatment to another dozen who have already been infected.
Data gathered in the first 17 days of March by Premier Inc., a large group purchasing organization for 4,000 U.S. hospitals, showed a 300 percent week-over-week increase in orders of chloroquine and a 70 percent week-over-week boost in orders of hydroxychloroquine.
“Both drugs are pretty much depleted right now in the distribution channel and wholesale distributors are reporting both products on back order,'' said Soumi Saha, senior director of advocacy at Premier.
In a typical month during 2019, sales of chloroquine to Premier’s 4,000 hospitals were 149 bottles of 100 pills, Saha said. In the first 17 days of March, those hospitals bought 2,357 bottles.
For hydroxychloroquine, those purchases were 16,000 bottles in the first 17 days of March, which is well more than twice the normal consumption, she said.
Those large purchases likely represented hospitals stocking up on supply, she added, so there may be more reserve inventory sitting on hospital pharmacy shelves.
In Massachusetts, one hospital, Boston Medical Center, said it ordered hydroxychloroquine early in the pandemic and is giving it to suspected coronavirus patients with breathing trouble.
The hospital reviewed emerging information about the use of the drug on the coronavirus in other countries and decided it would be prudent to try it in patients who are displaying signs of respiratory distress, said Dr. Tamar Barlam, chief of BMC’s division of infectious disease. The safety of the drug is well established, she said, and it could reduce the body’s dangerous inflammatory response to the virus. She said more than a dozen patients have been treated with the drug but that it’s too early to say if it has any benefit.
The drugs should be used exclusively in ill patients and not tried prophylactically by doctors and others, she said.
“The issue for me that’s disturbing is that people are getting their own prescriptions, or have prescribing rights, doctors or dentists, and writing themselves large prescriptions of the drugs, and doing it for themselves and family,'' she said. “If there’s hoarding, that is just going to be a big problem, and that is something that pharmacies and the health care system need to put a stop to pretty quickly.''
Much of the frenzy has been fueled by three recently published studies, on small groups of patients from China, Japan and France, that indicated possible benefits of the drugs. But those were not randomized clinical trials tested against a placebo, which is considered the gold standard for proof of efficacy.
Trump on Friday continued expressing optimism about the use of the drugs from the White House lectern, even as Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases, stood beside him trying to tamp down the hype. Fauci called the evidence thus far “anecdotal.''
“It was not done in a controlled clinical trial, so you really can’t make any definitive statement about it,'' Fauci said at a press briefing.
Later in the exchange, Trump said he has high hopes for at least one of the drugs: “It may work, it may not work. I feel good about it. That’s all it is. Just a feeling. You know, I’m a smart guy. I feel good about it. And we’re going to see.''
But with the run on the drugs, doctors warned of risks to lupus and rheumatoid arthritis patients.
There are no good alternatives, and withdrawal from the drugs can trigger new inflammatory flare-ups, said Dr. Karen Costenbader, director of the lupus program at Brigham and Women’s Hospital in Boston and the chair of the Lupus Foundation of America’s medical-scientific advisory council.
“These are essential long-term medications that are the foundation of treatment for many chronic and severe autoimmune diseases,'' she said. “There are already shortages and there is a lot of concern. Several pharmacies in the New England area have depleted their supplies already.''
Manufacturers of hydroxychloroquine include generic manufacturers Actavis, which is owned by Teva, and Sandoz. Novartis, the parent company of Sandoz, said it was prepared to donate 130 million doses of hydroxychloroquine around the world by the end of May, if its use is approved by governmental authorities. “The company is also exploring further scaling of capacity to increase supply and is committed to working with manufacturers around the world to meet global demand,” Novartis said.
Another generic company, Rising Pharmaceuticals, manufacturers both hydroxychloroquine and chloroquine. It recently reversed a doubling in prices that it imposed last year and said on Friday that it cut prices even further and would donate 1 million tablets in areas of greatest need.
“As it became clear in January that this growing crisis was upon us in the U.S., Rising Pharmaceuticals put these plans in motion to respond,'' said Ira Baeringer, Rising’s chief operating officer.
Bayer, the German drug giant, announced this week that it would donate 3 million tablets of its version of chloroquine to the U.S. government for a large clinical trial the FDA is considering.
Community pharmacists are reporting shortages of both drugs, as large purchases soak up existing supply, said Ronna Hauser, a pharmacist and the vice president of policy and government affairs operations at the National Community Pharmacists Association.
“The cascade effect is starting,'' she said.