Hydroxychloroquine has become one of the most talked about drugs in the coronavirus pandemic. While the old malaria drug shows the potential for future COVID-19 treatment, clinical trials are still underway to determine its exact efficacy and safety against the coronavirus.
Until more clinical trial data is available, patients, doctors, and hospitals around the globe should proceed with caution.
The Original Prescription Uses of Hydroxychloroquine
Hydroxychloroquine, also known under the brand name Plaquenil, was first approved for medical use in the U.S in 1955. Since that time, the drug has been prescribed to treat three main conditions:
- Acute attacks of malaria
- Discoid or systemic lupus erythematosus
- Rheumatoid arthritis
In order to prevent malaria in adults, patients must take two tablets of hydroxychloroquine once a week. The first dose is taken 7 to 14 days before traveling to high-risk malaria locations, and the doses are continued for 8 weeks following potential exposure. Treatment of acute malaria, on the other hand, requires an immediate dosage of four tablets, followed by two tablets 6 to 8 hours later and two tablets on each of the next two days.
Lupus and rheumatoid arthritis can both be treated with one or two tablets taken once or twice daily. As long as it’s taken on a consistent basis, hydroxychloroquine is proven to decrease the pain and swelling of arthritis and treat some symptoms of lupus.
Original clinical trials of hydroxychloroquine suggested that the drug’s possible side effects include headache, dizziness, loss of appetite, nausea, diarrhea, stomach pain, vomiting, and skin rash. Overall, the side effects of hydroxychloroquine have been well established since its FDA approval, leading the World Health Organization to include hydroxychloroquine on its List of Essential Medicines, a complete collection of “the most efficacious, safe and cost-effective medicines for priority conditions.”
Risks for Patients with Underlying Conditions
In more than six decades of use, hydroxychloroquine has typically been well tolerated by patients. Serious side effects are rare but possible, especially for patients with underlying conditions.
According to a fact sheet for patients distributed by the FDA, people with the following conditions may be at higher risk of complications after taking hydroxychloroquine:
- Patients with G-6-PD deficiency, porphyria, or other blood disorders
- Patients with eye problems involving the retina
- Patients with a history of seizures
- Patients with a heart condition including heart rhythm problems
Most notably, long-term use of hydroxychloroquine may increase the risk of cardiomyopathy and heart failure. Past cases include a 65-year-old man with heart failure who had been treated for eight years with hydroxychloroquine for rheumatoid arthritis. In another case, a 55-year-old woman with systemic lupus erythematosus (SLE) was diagnosed with heart failure after nine years of twice-daily hydroxychloroquine treatment.
Retina damage is also a concern for patients who rely on hydroxychloroquine to treat an autoimmune condition. However, eye damage is rare, with only about 1% to 2% of patients developing retinal problems during a 5-year treatment plan. Symptoms of retinal toxicity include trouble focusing on objects straight ahead, difficulty reading, blurry or distorted vision, and changes in color vision.
What Do the COVID-19 Clinical Trials Indicate?
As of April 7, the FDA lists 17 clinical trials enrolling and recruiting participants to study the effects of hydroxychloroquine on COVID-19. These trials are located throughout the United States and internationally and include teams led by the WHO, University of Pennsylvania, and more.
The first completed clinical trial took place in Marseilles, France. Of the 36 people studied by physician-scientist Didier Raoult and his team, 16 were infected controls and 20 were treated patients.
All 20 test patients received 600 mg daily of Plaquenil. By Day 3, half of the treated patients tested negative for the COVID-19 virus. By Day 6, a full 70% tested negative.
This clinical trial also used six patients to measure the effects of treating the coronavirus with a combination of Plaquenil and the antibiotic azithromycin. Of these six patients, five of them tested negative for COVID-19 on Day 3 and all six of them tested negative by Day 6.
These results were dramatically different than the infected control patients. Only 6.3% and 12.5% tested negative for COVID-19 on Day 3 and Day 6, respectively. In response to the findings of this clinical trial, the French Minister of Health approved new expanded treatment trials.
The Shanghai Public Health Clinical Center also sponsored a clinical trial in February 2020 to evaluate the efficacy and safety of hydroxychloroquine in the treatment of pneumonia caused by COVID-19. This randomized clinical trial studied 30 participants. Half of the participants received hydroxychloroquine treatment for five days plus conventional treatment, while the other half received conventional treatment only. After seven days, 13 patients treated with hydroxychloroquine tested negative for COVID-19, as did 14 patients in the control group.
As the study notes, “Larger sample size studies are needed to investigate the effects of hydroxychloroquine in the treatment of COVID-19.”
Drug Hoarding Impacts Patients Who Need It Most
As media headlines continue to suggest hydroxychloquine’s potential to treat coronavirus, an increasing number of doctors are attempting to hoard the drug. This presents an ongoing threat to the autoimmune disease patients who have relied on hydroxychloroquine for years and are now struggling to fill their prescriptions.
On March 16, the American Society of Health-System Pharmacists (ASHP) added hydroxychloroquine to its list of drugs in short supply. At the time, four of the medication’s eight manufacturers reported a shortage of the drug.
“It’s a challenge for us and for our patients,” explained Thomas Dörner, a rheumatologist at the Charité University Hospital in Berlin. “When I write a prescription now, I tell my patients they might need to go to several pharmacies before they get it filled.”
This is especially concerning for Lupus and Sjögren’s syndrome patients who have no other treatment alternatives; hydroxychloroquine is the only drug capable of successfully managing their condition. The decision by doctors and hospitals to hoard a drug still undergoing clinical trial testing may threaten their access to a critical medication.
In response, state pharmacy boards have started taking matters into their own hands. The National Association of Boards of Pharmacy reports that states including North Carolina, Ohio, Texas, and Nevada have implemented steps to limit inappropriate prescriptions for hydroxychloroquine and preserve supplies for patients who rely on it for their existing conditions.
CVS Health Corp and Express Scripts are also doing their part by placing limits on prescriptions of hydroxychloroquine. According to Express Scripts spokeswoman Jennifer Luddy, “We are seeing a surge in demand for these potential therapies, and are talking with manufacturers regularly about production.” Walgreens, meanwhile, has a 14-day limit for new prescriptions and a 30-day supply limit for refills.
Sources
- https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001837/
- https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Hydroxychloroquine-Plaquenil
- https://www.fda.gov/media/136538/download
- http://www.onlinejacc.org/content/71/11_Supplement/A2395
- https://www.aao.org/eye-health/tips-prevention/covid-chloroquine-hydroxychloroquine-plaquenil
- https://clinicaltrials.gov/ct2/results?cond=COVID-19&intr=%22Hydroxychloroquine%22&recrs=a&recrs=f&recrs=d&recrs=e&age_v=&gndr=&type=Intr&rslt=&Search=Apply
- http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03