COVID-19 experimental therapies and TdP Risk

March 20, 2020 at 6:12 AM

Like you, we at CredibleMeds are adjusting to the many disruptions in our daily lives that are now necessitated by the COVID-19 pandemic.  We hope you and your loved ones are safe and remain healthy. At this time, drastic measures and innovative approaches are needed and can be justified, but one area under investigation requires a special caution. Several of the medicines now being tested for efficacy in the treatment of COVID-19 are on the list of drugs known to have a risk of Torsades de Pointes (TdP) arrhythmia.  These include the antimalarials, chloroquine or hydroxychloroquine, that are being combined with azithromycin or with the antivirals, lopinavir/ritonavir.  Each of these drugs alone can cause QT prolongation and chloroquine, hydroxychloroquine and azithromycin are on the CredibleMeds’ list of drugs known to cause TdP.

These drugs, especially if used in these combinations, require careful monitoring of the QT interval and full awareness of risk factors such as the other QT-prolonging drugs that might be co-administered. In addition to the drugs’ direct effects on the QTc, there is a very high likelihood that their metabolic interactions will contribute to a greater risk of cardiac toxicity. Furthermore, the risk of TdP may be even higher because these combinations are being tested in the most ill patients, i.e. the elderly who are more likely to have cardiac disease or other TdP risk factors.

For those investigating these drug combinations, we recommend a screening ECG with QTc evaluation, avoidance of any non-essential QT-prolonging drugs, correction of any electrolyte imbalance before administration and close QTc monitoring during therapy.

We encourage all healthcare providers to be aware of the potential risk of TdP with these drugs and to refer frequently to the QTdrugs lists as they care for their patients and fight to control this pandemic.




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Posted by Diana0324 on
Thank you for keeping us informed. In many occasions the medical personnel in the hospital doesn't know about LQTS.
Posted by etzainea on
Dr. Wosley, I know I should say thank you for the vital information but under the circumstances it's not welcome news! I started self-isolating a week ago and "following all the rules." I am hoping I can stay well. I have CLQT 2 which I learned about at age 66 because of a family member. I have never had an incident. I take 25 mg metoprolol daily and no drugs that prolong QT. I am 72 in good health. This is not good news in a week of bad news! I am not sure I understand. Am I correct that it would be a doctor's decision to try one or some of these drugs in a worse case scenario with the monitoring you describe? Are there any other drugs that you know of being considered for treatment that do not affect the QT interval? I guess the best thing at this point is to print this report and give it to a provider if I should get sick. I'm not even sure if older adults can recover without hospitalization!
Thank you
Ellen
Posted by rwoosley on
Ellen, Thank you for your email and for your efforts to stay safe and help protect others. I hope you are not discouraged since there are many drugs being tested and some of those do not prolong QT. We are working to inform the healthcare community about the many drugs such as some of those now being tested when it would be prudent to take special precautions for their safe use. It will be some time before we know which of these medicines are effective and whether they are safe. It is almost a certainty that any therapy that is found to be effective will require a doctor's prescription and supervision. We at AZCERT will be monitoring the available data on these drugs and work to help inform everyone about the safe use of these and other medications being tested for COVID-19.
Posted by fmarber on
Dr Wosley,

thanks a lot for the webpage and your post. Do you know if there is any experience or concerns about the antivirals, tht probably Will be used, against Covid-19 next weeks. For example, favipiravir and remdesivir. I am afraid that probably not, because it is too early.

Best regards and thanks a lot,

Franz Martín
Posted by rwoosley on
Ray Woosley Thank you for your question. At this time, there is no drug treatment that is proven to be effective or that has been approved by regulatory agencies to treat COVID-19. Several antivirals (including favipiravir, remdesivir and lopinavir/ritonavir) and antiinflamatory drugs (azithromycin) and antimalarials (chloroquine and hydroxychloroquine) are now being tested in clinical research for their potential benefit. Chloroquine, hydroxychloroquine, azithromycin and lopinavir/ritonavir) are known to prolong QTc. All patients, especially those with cLQTS, should only take those drugs if they and their doctors have thoroughly considered the potential benefits and risk. Also, we recommend QTc monitoring for all patients receiving these drugs for COVID-19, especially if they are being given in combination. Since remdesivir and favipiravir are not approved in the US, we cannot find many studies or data to review for their safety. There are no reports of QT prolongation or arrhythmias reported in the NLM PubMed database at this time. A study from Japan examined favipiravir for effects on QTc in normal subjects and did not find any prolongation. We always point out that such studies exclude patients with long QT so we cannot be absolutely sure how patients with cLQTS would respond. I hope this is helpful. Ray Woosley
Posted by jilleallen on
Thanks, Dr. Woosley. I can always count on you and your associates for a thoughtful, thorough, and timely assessment of a complex issue.

BTW I appreciate the addition of cesium chloride to the known torsades list. It is still being touted on the internet as cancer therapy and is accessible.
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