Hydroxychloroquine and COVID-19

Various drugs are used off-label to treat COVID-19, a lung disease caused by SARS-CoV-2, and it is hoped that these will have a positive influence on the course of the disease. However, no therapy to date has been proven effective.

Hydroxychloroquine is an active substance approved in Switzerland for the treatment of rheumatological diseases (chronic polyarthritis, lupus erythematosus), certain skin diseases (photodermatoses) and malaria prophylaxis and therapy. Currently, the product is also increasingly used off-label for COVID-19 treatment, based mostly on in vitro (Yao et al., 2020) and limited clinical data with inconclusive results with varying hydroxychloroquine dosages and combinations (e.g. Gautret et al., 2020, Molina et al., 2020, Chen et al., 2020, Mégarbane, 2020). In spite of these uncertainties, an increase in the use and prescription of hydroxychloroquine has been seen in the recent weeks, including cases of self-medication. In view of the increased use of the substance as well as the great media attention, we warn of the potential dangers of this active substance. Hydroxychloroquine can have serious side effects, especially at high doses or when combined with other medicines (Ferner & Aronson, 2020). Overdoses can result in even fatal poisoning with cardiac arrest. Children in particular can develop severe symptoms even after accidental intake of a single tablet.

Serious adverse effects include:

  • cardiovascular: QT prolongation with torsades de pointes arrhythmias (especially in combination with other QT-prolonging drugs such as azithromycin or when a QT-prolongation is present before start of the drug intake); for further information on QT-prolonging drugs, see the link regarding QTc-prolongation by drugs in the link collection on our COVID-19 webpage
  • endocrine: severe hypoglycemia
  • hematologic: agranulocytosis, anemia, pancytopenia
  • hepatic: fulminant liver failure
  • musculoskeletal: disorder of muscle
  • neurologic: extrapyramidal disorders
  • ophthalmic: retinal disorder

Selected Drug-Drug interaction:

  • QT-prolonging agents (e.g. azithromycin) may enhance the QTc-prolonging effect of hydroxychloroquine

Hydroxychloroquine must not be used by patients without a prescription and without supervision by a doctor. Prescriptions should not be given outside their authorised uses except in the setting of a clinical trial or nationally agreed protocols. Hydroxychloroquine should only be used in the dosage prescribed. Self-medication or passing on to family and friends for therapy of COVID-19 is clearly not recommended. To avoid accidental ingestion, parents should be reminded, to keep the preparations out of the reach of (young) children.

  • For questions about coronaviruses, you can obtain further information from the Federal Office of Public Health FOPH's Coronavirus Infoline +41 58 463 00 00 (24 hours a day).
  • For questions regarding drug-drug interactions, adverse drug reactions, therapeutic monitoring you can contact the Departments of Clinical Pharmacology in Basel, Bern, Geneva, Lausanne, Ticino and Zurich.
  • If you have any questions about poisoning and overdoses and their therapy, Tox Info Suisse is available 24/7 via the emergency number 145.

(written by Stefan Weiler, MD, PhD, member of the SSCPT executive board, on April 15, 2020)

References

  • Yao X, Ye F, Zhang M, et al. 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). Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa237
  • Gautret P, Lagiera JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. DOI: 10.1016/j.ijantimicag.2020.105949
  • Mégarbane B. Chloroquine and hydroxychloroquine to treat COVID-19: between hope and caution. Clin Toxicol (Phila). 2020 Apr 2:1-2. DOI: 10.1080/15563650.2020.1748194
  • Molina JM, Delaugerre C, Goff JL, et al. No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection Med Mal Infect. 2020 Mar 30. pii: S0399-077X(20)30085-8. DOI: 10.1016/j.medmal.2020.03.006
  • Chen J, Liu D, Lui L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 COVID-19). Journal of Zhejiang University 2020; 03-03
  • Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020; 369:m1432. DOI: 10.1136/bmj.m1432.