Hydroxychloroquine COVID-19 Drug Interactions

As we learn more each day about how best to beat SARS-CoV-2 (Corona Virus/COVID-19), hydroxychloroquine keeps being included in the discussion. While the interest in this drug is exploding, we have to be mindful of the potential hazards of the drug. Fortunately, we have a long history of knowledge with this drug, just for the treatment of malaria and rheumatologic disorders. Today, let’s focus on one issue – drug interactions

While other toxicity issues with hydroxychloroquine are concerning, much of their data surround use in malaria and other rheumatologic diseases where doses could exceed 5 mg/kg/day for an extended period of time. But from our growing knowledge of the use of hydroxychloroquine in SARS-CoV-2 is a much shorter course of 10 days. What is not likely to change based on the relatively short course is that hydroxychloroquine is a CYP 2D6 inhibitor, which can lead to numerous drug interactions.

In fact, these drug interactions can be long-lasting beyond the end of therapy owing to hydroxychloroquine’s long half-life. We know that after giving a single 200 mg oral dose of hydroxychloroquine men, the mean half-life was about 22 days. {PI} This likely means that the drug interaction potential could be long-lasting as well. 

There are numerous concerning drug interactions:

  • Increased digoxin concentration/toxicity
  • Enhanced hypoglycemic effects from insulin as well as other agents (sulfonylureas)
  • Everything that prolongs QT interval (ondansetron, droperidol, clarithromycin)
  • Decreases seizure threshold and increases the likelihood of antiepileptic failure. Some (phenytoin, carbamazepine, phenobarbital) may increase the metabolism of hydroxychloroquine

Yet there are more interactions that may be more difficult to identify, particularly in monitoring patients in an outpatient setting (assuming we may be dispensing hydroxychloroquine in that setting). SSRIs (fluoxetine, paroxetine) SNRIs (venlafaxine, duloxetine), opioids (codeine, oxycodone, hydrocodone, tramadol), and metoprolol all have potentially significant interactions via 2D6 with hydroxychloroquine. Monitoring for serotonin syndrome, opioid toxicity, and beta-blocker toxicity and providing extensive counseling on these risks should be a key component to patient education with hydroxychloroquine.

There continue to be new developments each day with our knowledge of how to defeat SARS-CoV-2. We will prevail. Let’s keep sharing knowledge, and refining our understanding of the treatments and prevention.

Update: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial 

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