Food and Drug Administration Issues Approval

Food and Drug Administration Issues Approval for Widespread Use of Chloroquine and Hydroxychloroquine

Nola Curry, PharmD

Food and Drug Administration Issues Approval for Widespread Use of Chloroquine and Hydroxychloroquine

 

As of March 12th, 2020, the novel coronavirus, SARS-CoV-2, was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 is a highly contagious RNA virus spread from person to person through respiratory droplets and contact with the virus on surfaces. Symptoms of infection range from mild to severe and can even cause death. Symptoms appear anywhere from 2-14 days after exposure and can include fever, dry cough, and shortness of breath. In critical cases, symptoms include trouble breathing, pain and/or pressure in the chest, altered mental status, and cyanosis as the patient develops pneumonia. Unfortunately, due to their age and multiple comorbidities, hospice patients make up the most vulnerable population at risk for developing a severe case of coronavirus disease 2019 (COVID-19).

The number of infected Americans has now surpassed the amount in any other country with new cases climbing exponentially. Our healthcare providers are at the frontline battling this pandemic with many challenges. There is an urgent need to work together globally to expand testing, contain infected persons, and find a safe and effective way to manage the disease caused by this virus.

On March 28, 2020, in an effort to help ease the destruction of the pandemic, the United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the utilization of oral chloroquine phosphate and oral hydroxychloroquine sulfate to treat severe cases of COVID -19 in hospitalized adolescent and adult patients. Currently, there is no FDA approved medication for this indication, but the use of hydroxychloroquine, with or without the antibiotic Azithromycin, has been used in other countries with reported benefits. Many health experts warned against the widespread use of these medications due to the lack of a robust clinical trial demonstrating clinical improvement and safety.

Chloroquine, and its derivative hydroxychloroquine, are antimalarial agents with immunomodulation effects approved for the use of malaria, rheumatoid arthritis, and systemic and discoid lupus erythematosus. In one in vitro study in China, both agents were shown to have antiviral effects with hydroxychloroquine being more potent with a more tolerable safety profile. Common side effects of these agents include headache, dizziness, GI upset, nausea and vomiting, skin/hair discoloration, and hair loss. More severe side effects include liver impairment, severe hypoglycemia, muscle weakness, QT prolongation, skin rash, and bone marrow suppression. The use of these agents is contraindicated in the presence of retinal or visual field changes of any etiology and patients with known hypersensitivity to 4-aminoquinoline compounds. These agents should not be used in patients with a prolonged QT interval at baseline or increased risk for arrhythmia due to heart disease.

Recommended dosing for hydroxychloroquine is 800 mg by mouth on day 1, then 400 mg daily for four to seven days. Recommended dosing for chloroquine is 1 gram on day 1, then 500 mg daily for four to seven days. The suggested dose and duration may be updated as information from ongoing clinical trials become available.

To mitigate the risk associated with using these agents for an unapproved use, mandatory requirements have been implemented and all must be met before the administration of either product. These requirements include:

  1. Patients must be adolescents or adults who weigh at least 50 kg (110 pounds) and are hospitalized with COVID-19 for whom a clinical trial is not available.
  2. A Fact Sheet for Patients or Caregiver must be discussed with the patient or caregiver. The information on this fact sheet assists the patient to understand that the use of these agents is unapproved by the FDA. It also reviews contraindications, adverse side effects, and drug interactions.
  3. Providers must provide requested feedback to the FDA for information about adverse events and medication errors following the receipt of these agents.
  4. Providers are expected to report information about adverse events and medication errors to FDA MedWatch within 7 calendar days from the onset of the event.

Numerous active clinical trials are underway in multiple countries as scientists and healthcare providers work together to develop protocols to manage COVID-19 and provide prophylaxis therapy for post-exposure. Many hospice patients may not qualify for the use of chloroquine and hydroxychloroquine. In these cases, supportive care and symptom management remain our best options. As health care providers it is imperative that we stay current with the most up to date information as medicine is evolving daily.

 

 

References:

  1. “Coronavirus.” World Health Organization, World Health Organization, 12 Mar. 2020, who.int/emergencies/diseases/novel-coronavirus-2019.
  2. “Symptoms of Coronavirus.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 20 Mar. 2020, cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.
  3. Commissioner, Office of the. “Emergency Use Authorization.” S. Food and Drug Administration, FDA, 28 Mar. 2020, www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov.
  4. Xueting Yao, Fei Ye, Miao Zhang, Cheng Cui, Baoying Huang, Peihua Niu, Xu Liu, Li Zhao, Erdan Dong, Chunli Song, Siyan Zhan, Roujian Lu, Haiyan Li, Wenjie Tan, Dongyang Liu, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clinical Infectious Diseases, , ciaa237, https://doi.org/10.1093/cid/ciaa237
  5. Gautret, Philippe, et al. “Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial.” International Journal of Antimicrobial Agents, U.S. National Library of Medicine, 20 Mar. 2020, ncbi.nlm.nih.gov/pubmed/32205204.
  6. Lexi-Drugs Online. Lexicomp. Wolters Kluwer; Hudson, OH. Accessed March 28, 2020