Chloroquine, Hydroxychloroquine, and/or Azithromycin for COVID-19

Quick Takes

  • The Scientific Medical Policy Committee of the American College of Physicians recommends that we should NOT use chloroquine or hydroxychloroquine alone or in combination with azithromycin as prophylaxis against COVID-19 due to known harms and no available evidence of benefits in the general population.
  • They also recommend that we should NOT use chloroquine or hydroxychloroquine alone or in combination with azithromycin as a treatment of patients with COVID-19 due to known harms and no available evidence of benefits in patients with COVID-19.
  • In light of known harms and very uncertain evidence of benefit in patients with COVID-19, using shared and informed decision making with patients (and their families), clinicians may treat hospitalized COVID-19–positive patients with chloroquine or hydroxychloroquine alone or in combination with azithromycin in the context of a clinical trial.

Study Questions:

Should clinicians use chloroquine or hydroxychloroquine alone or in combination with azithromycin for the prophylaxis or treatment of coronavirus disease 2019 (COVID-19)?

Methods:

These practice points are based on a rapid and living systematic evidence review conducted by the University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and will be updated as new evidence becomes available. This version is based on an evidence review conducted on April 17, 2020, and was approved by the American College of Physicians Board of Regents on May 4, 2020, and submitted to Annals of Internal Medicine on May 6, 2020. It was published at Annals.org on May 13, 2020. The practice points development and update methods are included in the appendix available at Annals.org.

Results:

At the time of the review, there were no published studies or available evidence to suggest that chloroquine, chloroquine and azithromycin, hydroxychloroquine, or hydroxychloroquine and azithromycin should be used as prophylaxis against COVID-19 in the general population. There were 10 studies (three randomized controlled trials [RCTs], three cohort studies, and four case series) examining treatment. Only two RCTs were deemed to have a low risk of bias; one was determined to have a high risk of bias. Two cohort studies were deemed to have a critical risk of bias and one was deemed to have a moderate risk of bias. Quality was not assessed for the four case series. In total, 1,758 COVID-19–positive patients were included in this analysis with an average age ranging from 37-63 years; approximately 52% were male. There was variability in severity of and existing comorbidities. Six of these studies examined hydroxychloroquine and four examined hydroxychloroquine and azithromycin. From a geographical perspective, there were five studies performed in France, three in China, and two in the United States.

Known harms of chloroquine in patients without COVID-19 include (but are not limited to): cardiovascular (cardiomyopathy, electrocardiographic changes); hematologic (aplastic anemia, thrombocytopenia); nervous system (seizures, psychosis, extrapyramidal disorders); and ophthalmic macular degeneration. Known harms of hydroxychloroquine in patients without COVID-19 include (but are not limited to): cardiovascular (cardiomyopathy, cardiac failure, ventricular arrhythmias, torsade de pointes); endocrine (hypoglycemia); hematologic (aplastic anemia, thrombocytopenia); nervous system (seizures, psychosis, extrapyramidal disorders); and ophthalmic macular degeneration. In the evidence reviewed, hydroxychloroquine doses did not exceed 600 mg daily for 5-10 days. Inappropriate and overuse of antibiotics (e.g., azithromycin) is an important contributor to antibiotic resistance, which is an immediate public health threat.

Conclusions:

The efficacy of chloroquine or hydroxychloroquine alone or in combination with azithromycin to prevent COVID-19 after infection with SARS-CoV-2 or to treat patients with COVID-19 is not established. There are known harms of these medications when used to treat other diseases.

Perspective:

These practice points from the Scientific Medical Policy Committee of the American College of Physicians synthesize the best available evidence as of April 17, 2020. The authors concluded that the current evidence about efficacy and harms for use in the context of COVID-19 is sparse, conflicting, and from low-quality studies. At this time, this committee does not support the use of chloroquine or hydroxychloroquine alone or in combination with azithromycin for prophylaxis against or treatment of COVID-19. Future clinical trials are needed.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Statins

Keywords: Antibiotic Prophylaxis, Arrhythmias, Cardiac, Azithromycin, Cardiomyopathies, Chloroquine, COVID-19, Coronavirus, Critical Care, Hematology, Hydroxychloroquine, Hypoglycemia, Macular Degeneration, Patient Harm, Primary Prevention, Risk Assessment, severe acute respiratory syndrome coronavirus 2, Treatment Outcome


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