Toxicities of Hydroxychloroquine
by Dr. David Borenstein M.D. 4/2020
Hydroxychloroquine is a close relative of chloroquine, a drug that was used during WWII for preventing malaria and as therapy for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The mechanism of action as described with changing the pH in specific structures in cells which alters the hyperimmunity of RA and SLE patients is the suggested mechanism the replication of the coronavirus is inhibited. A variety of clinical trials have been initiated to determine if hydroxychloroquine would be effective in healing COVID-19 patients. The dose of hydroxychloroquine prescribed for RA and SLE patients is 200 to 400 mg a day. Chloroquine is prescribed rarely at a 250 mg per day dose.
A trial in Brazil utilizing chloroquine was halted because of cardiac deaths. Chloroquine was given at a dose of 450 milligrams twice a day for five days or at 600 mg for 10 days. Within three days, abnormal heart rhythms were noted in the patients receiving the higher dose of chloroquine. By day six, 11 patients had died from heart rhythm problems. The study with high dose chloroquine was discontinued.
Another study from China reported on the use of hydroxychloroquine at a dose of 1200 mg for 3 days followed by 800 mg daily for 2 weeks for mild symptoms and 3 weeks for severe symptoms versus a group who received supportive care. The outcomes were similar in both groups independent of receiving hydroxychloroquine or not. The toxicity rate was 8 % in the placebo group and 30% in the hydroxychloroquine group. No mention was made of cardiac issues but no results from electrocardiograms (EKG) were presented.
The results from these studies should give us some pause in regard to the overall benefit of hydroxychloroquine and chloroquine for the treatment of Covid-19 infection. High doses of these medicines may prolong the QT interval on the EKG. Basically, the electrical signals that supply the heart are disorganized resulting in irregular beats. If the beats are not regularized, the heart will stop working, resulting in sudden death.
Under these circumstances, chloroquine and hydroxychloroquine do not seem to be the prime candidates for resolving coronavirus 19 infections. Other therapies, such as Remdesivir and tocilizumab, are under active investigation in clinical trials and show initial potential as effective agents. The results of these investigations should be available within a month or two. Until then, physically distancing, and hand washing remain the prime means of limiting the spread of COVID-19.