Last update and review: July 8, 2020.
Introduction.
The combination of hydroxychloroquine (HCQ) and azithromycin (AZ) showed some effectiveness as a treatment for COVID-19. However, HCQ+AZ should not be considered as a “wonder drug” or “panacea” for COVID-19.
There have been a number of studies on the use of HCQ or HCQ+AZ for the treatment of COVID-19. Most of them are of poor quality and were conducted in hospitals with high levels of medical malpractice.
The group of Didier Raoult at the IHU hospital in Marseille, France, produced a rare set of reliable data on the treatment of COVID-19.
The group of Didier Raoult at the IHU hospital in Marseille, France, produced a rare set of reliable data on the treatment of COVID-19. HCQ+AZ was the preferred treatment for COVID-19 at the IHU and the results in terms of mortality and other outcomes were good. However, the IHU hospital in Marseille, France, is a pole of excellence in the treatment of infectious disease. It is, therefore, difficult to determine what explains the good results, the general clinical excellence or the use of HCQ+AZ.
For the majority of COVID-19 patients, there are definitely at least some benefits of the HCQ+AZ treatment.
We have been reviewing the results of HCQ+AZ treatment at the IHU hospital in Marseille, France. We will be publishing our analysis in other articles on this website. But in short, our current opinion is that, for the majority of COVID-19 patients, there are definitely at least some benefits of the HCQ+AZ treatment.
The IHU hospital in Marseille, France, is a pole of excellence: use their recommendations.
There are some contra-indications for the HCQ+AZ treatment. Also, patients need to be screened for potential prolongation of QT time on electrocardiogram and for electrolyte balance. Given that the IHU hospital in Marseille, France, is a pole of excellence, we recommend using their pre-therapy workup and the follow-up recommendations. The summary and the references are below.
HCQ+AZ, the protocol, the pre-therapy workup and the follow-up in the IHU hospital in Marseille, France.
“200 mg of oral hydroxychloroquine (HCQ), three times daily for ten days with five days of azithromycin (AZ) (500 mg on day 1 followed by 250 mg daily for the next four days).”
Millon et al., 2020 (1):
Patients with no contraindications were proposed a combination of 200 mg of oral HCQ, three times daily for ten days combined with five days of AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Therapy was not supervised. No children <14 years, pregnant women or patients with G6PD deficiency (based on patient’s declaration only) were included.
The pre-therapy workup: electrolytes, electrocardiogram with corrected QT (Bazett’s formula).
Drugs with potential to prolong QT or non-vital potassium depleting drugs (diuretics) were stopped.
If hypokalaemia at admission, or potassium-depleting drugs could not be stopped, potassium supplementation was provided.
Electrolyte monitoring in patients with low potassium at baseline.
Millon et al., 2020 (1):
The systematic pre-therapy workup included serum electrolyte analysis, and an electrocardiogram with corrected QT measurement (Bazett’s formula). A specific inclusion protocol and follow-up for torsade de pointes risk was designed. Any drug, being used by the patient, with the potential to prolong the QT interval and non-vital potassium depleting drugs (diuretics prescribed for high blood pressure) were systematically stopped. When potassium-depleting drugs could not be stopped or in case of documented hypokalaemia at admission, potassium supplementation was provided and HCQ was administered only when the potassium level was normalized. Close serum electrolyte analysis monitoring was performed in patients with low serum potassium levels at baseline.
An electrocardiogram 48 hours after the start of treatment: if QT>500ms, HCQ discontinued. If 460ms<QT<500ms, a risk-benefit of HCQ+AZ was decided.
Millon et al., 2020 (1):
An electrocardiogram was routinely performed 48 hours after the start of treatment. Treatment with HCQ was discontinued when the corrected QT interval (QTc, Bazett’s formula) was > 500ms and the risk-benefit ratio of HCQ+AZ treatment was estimated by the infectious disease specialist and agreed with the cardiologist, at between 460 and 500ms. The indications for this control ECG were restricted after an initial workup in 848 ECG from 424 patients (at 8 day 0 and day 2 for each patient) showing that all contraindicative repolarization abnormalities had been detected on the first ECG. HCQ dosage was performed as previously described [14,21] and a concentration of > 0.1 µg/mL was considered in the therapeutic range [ 22]. Broad spectrum antibiotics (ceftriaxone or ertapenem) were added for patients with pneumonia and NEWS-2 score ≥5. Symptomatic treatments, including notably oxygen, were added as needed.
In the study by Lagier et al., 2020 (3), of the total of 3337 patients who received HCQ+AZ, only 20 (0.6%) had clinically significant prolongation of QT.
In the study by Lagier et al., 2020 (3), of the total of 3337 patients who received HCQ+AZ, only 20 (0.6%) had clinically significant prolongation of QT. Among the patients who received either HCQ alone or AZ alone, 2% and 2.2% respectively, had clinically significant prolongation of QT.
Contra-indications to hydroxycloroquine and azithromycin as described by Gautret et al., 2020 (2).
Gautret et al., 2020 (2):
Hydroxychloroquine
Absolute contraindications to hydroxychloroquine include known hypersensitivity to hydroxychloroquine or chloroquine, amino-4 quinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, retinopathy, age < 6 years, lactation, patients taking citalopram, escitalopram, hydroxyzine, domperidone, and piperaquine because of increased risk of arrhythmia and torsades de pointes. Relative contraindications or cases in which it is not recommended include cases of hepatic porphyria, hypersensitivity to lactose, abnormalities of galactose metabolism, lactase deficiency, and digestive malabsorption / intolerance syndrome due to the presence of lactose as an excipient.
Azithromycin
Absolute contraindications to azithomycin include known hypersensitivity to azithromycin, erythromycin, chlarithromycin, dirithromycin, josamycin, midecamycin diacetate, roxithromycin, telithromycin, macrolides, ketolides, everolimus, pimecrolimus, sirolimus, temsirolimus, fidaxomicine, peanut oil and soy. Contraindications also include pseudomembranous colitis, anaphylactic shock, severe skin involvement, acute exanthematic pustulosis, DRESS syndrome, severe liver failure, patient taking colchicine, cisapride, dihydroergotamine and ergotamine. Use is not recommended for patients with cholestase, or who are taking bromocriptine, cabergoline, lisuride and pergolide. It is not recommended in cases of hypersensitivity to lactose, abnormality of galactose metabolism, lactase deficiency, and digestive malabsorption / intolerance syndrome due to the presence of lactose as an excipient. Source: Theriaque: independent-drug database for good use of drugs by health practitioners. Husson MC. Ann Pharm Fr. 2008 Nov-Dec;66(5-6):268-77. 5. http://www.theriaque.org
How to use this text.
If you are a patient.
A COVID-19 patient who considers starting HCQ+AZ treatment may want to print this text and to take it to his or her medical practitioner. Additional information can be found in the referenced articles.
If you are a medical practitioner.
If you are a medical practitioner, you need to review the information in the referenced articles as well as other sources in order to make sure that patients are receiving the HCQ+AZ treatment safely.
A Test: How many patients died in the ICU in the “No HCQ-No Az” group?
To understand if HCQ+AZ treatment was effective, it may be useful to know how many patients died in an ICU and how many died without being admitted to an ICU.
Use the data in the table below and calculate How many patients died in the ICU in the “No HCQ-No Az” group.
How to use this test.
Only people who have a habit of using logic can navigate a subject on which most of the information is confusing or contradictory. The effectiveness of HCQ+AZ is one such subject. Simple short tests like the one above help to identify medical practitioners who can understand data and use logic.
Selected references:
1. Million et al. (the group of Didier Raoult). Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Medicine and Infectious Disease Volume 35, May–June 2020, 101738.
2. Gautret et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study Author links open overlay panel. Travel Medicine and Infectious Disease Volume 34, March–April 2020, 101663.
3. Lagier et al. Travel Medicine and Infectious Disease(2020).
2 Comments