Hydroxychloroquine for SARS-CoV-2

Not too long ago (last week), social media was a major divider in society. What is has become in just a few short days is simply incredible. We are observing an incredible collective effort to learn more about SARS-CoV-2, inform each other, and provide a few moments of levity. With each day we are learning more about SARS-CoV-2 from physicians, scientists, billionaires, and the patients themselves.

One of these incredible insights is the potential use of hydroxychloroquine for SARS-CoV-2. While the evidence is understandably limited for its use in this novel infectious disease, we can take a look at it once again since hydroxychloroquine is not commonly encountered in many clinical settings.

What is hydroxychloroquine?

Hydroxychloroquine, a β-hydroxylated chloroquine based structure, is a relatively commonly used drug for Malaria. Its antimalarial properties are multifaceted but primarily involve increasing the pH of intracellular compartments causing suppression of T-cell activation and prevention of leukocyte chemotaxis. What’s interesting from an antiviral (and specifically SARS-CoV-2) is its ability to inhibit DNA and RNA synthesis.

In this action, hydroxychloroquine may impact the cell membrane surface pH, and disrupt the virus from fusing to the cell membrane itself. Additionally, both chloroquine and hydroxychloroquine have immunomodulatory effects by potentially inhibiting IL-6 and IL-10 that can mediate the potential “cytokine storm” that has been reported related to SARS-CoV-2. There are numerous other potential mechanisms at play that are not fully described or substantiated. Nonetheless, the pharmacology is promising.

What’s the dose for SARS-CoV-2?

Based on an animal model recently published, hydroxychloroquine should be given as a loading dose followed by a maintenance dose.

  • Loading dose: 400 mg PO BID
  • Maintenance dose: 200 mg PO BID x 4 days

Hydroxychloroquine Safety

Although this seems like a promising therapy, there are notable adverse events and drug interactions to remember.

Since hydroxychloroquine is a sodium and potassium channel blockade, cardiovascular toxicity is a concern. Concerning arrhythmias can include QRS complex prolongation, AV block, ST and T wave depression, increased U waves, and QT interval prolongation. These arrhythmias can be further complicated by another common adverse event: hypokalemia. Since this hypokalemia is really a shift of potassium, and not truly a depletion, cautious supplementation is necessary to avoid hyperkalemia.

Central neurologic manifestations can also be problematic. The range of effects can include CNS depression, dizziness, headache, and progress to convulsions, dystonic reactions and transient parkinsonism.

Other notable toxicities include hemolysis in G6PD-deficient patients, retinal damage, sensorineural deafness, and hypoglycemia. With regards to the ophthalmologic toxicities of hydroxychloroquine, they rarely occur at doses lower than 6.4 mg/kg/d. However, patients who have a lowe body weight, and either renal or hepatic impairment, where their risk of retinal damage is high, ophthalmologic exams should be conducted frequently.

In pregnant patients, hydroxychloroquine appears to be compatible with pregnancy. There is no evidence to suggest that there is an increased risk of birth defects or ocular toxicities.

While our understanding of SARS-CoV-2 continues to evolve, this information may become insufficient to continue operating on. I’ll do my best to keep updating it, as I am learning and relearning many of these interventions myself.

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