COVID‐19 and (hydroxy)chloroquine–azithromycin combination: Should we take the risk for our patients?

Abstract

The coronavirus disease 2019 pandemic has caught the scientific community and hospitals off-guard, and the race is on as clinicians grapple with novel treatment strategies and constantly changing recommendations. Patients with mental health disorders are particularly vulnerable to the coronavirus outbreak for various reasons, including cognitive impairment, little awareness of risk, diminished efforts regarding personal protection and more barriers in accessing timely health services. 1Only few therapeutic options are being tested for COVID-19 with no evidence yet of effectiveness or safety. One of the options presently under evaluation is the combination of (hydroxy)chloroquine with azithromycin. 2 Despite the limited clinical data on the use of (hydroxy)chloroquine in COVID-19, this drug is attracting considerable attention from the media. Individuals and lobby groups have called for widespread prescription of these drugs. This attention is undermining the structured approach with which any drug should be evaluated.In this rapidly evolving situation, we need to alert prescribers that the extensive use of (hydroxy)chloroquine-azithromycin would place patients, and particularly those with mental health conditions, at an important increased risk of QTc-prolonging and, consequently, torsade de pointes (TdP) and death. Only a few clinical studies have analysed the cardiovascular effects of these drugs, 3 although they are clearly acknowledged with a known risk for QTc-prolonging according to CredibleMeds (on the list 1 of drugs with a known risk for TdP).CredibleMeds provides the American official lists of drugs associated with a risk of QTc-prolongation, powered by international pharmacovigilance data. 4,5 However, patients with mental health problems are already highly exposed to the risk of increased QT for a number of reasons. First, many psychoactive substances are associated with an increased risk of QTc-prolonging, such as antipsychotics (chlorpromazine, levomepromazine, haloperidol, pimozide, sulpiride, sultopride and thioridazine), antidepressants (citalopram and escitalopram), methadone, cocaine or donepezil. Second, our patients have often numerous comorbidities and underlying risk factors making cases of COVID-19 more challenging to treat. For instance, patients on antipsychotics are more likely to be men, at a higher risk of obesity, hypertension, metabolic syndrome and for more serious health outcomes. Moreover, their sedentary lifestyle and other risk factors, such as smoking and poor diet, put them at an elevated risk of respiratory failure and early death. Thus, a careful and thorough assessment of risk factors is crucial in these patients, including sex, age, smoking, acute electrolytes disturbances, metabolic syndrome, cardiac and pulmonary disease.The COVID-19 pandemic calls for rapid testing of new treatment strategies. However, special care is needed when treating vulnerable populations. If the combination of (hydroxyl)chloroquineazithromycin is recommended in the near future for COVID-19, we ...

Drug–Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy

“…The most frequent potential adverse event was cardiac toxicity (increased risk of QT prolongation), which alone accounted for almost 90% of the predicted DDIs during hospitalisation. This is not unexpected because the cardiovascular safety of the drugs currently used to treat SARS-CoV-2 infection is still a subject of debate in the scientific community [ 13 – 15 , 27 – 30 ]. Some of the concern is due to the observation that patients with COVID-19 are at increased risk of developing cardiovascular diseases regardless of treatment because the reported decrease in potassium levels can cause electrocardiographic changes such as a prolonged QT interval [ 27 – 30 ].…”

“…Half of the patients with COVID-19 enrolled in the study were aged > 65 years, the threshold for assessing PIMs and the ACB established by consensus guidelines [ 15 – 17 ]. Using the updated Beers criteria, we found that the large majority of our patients had at least one PIM, with no difference between admission and hospitalisation.…”

“…The HIV protease inhibitors lopinavir and darunavir (the first drugs tested as SARS-CoV-2 inhibitors) are co-administered with the pharmaco-enhancers ritonavir or cobicistat, both of which are known to be responsible for pharmacokinetic-related DDIs because of their modulatory effects on cytochrome and non-cytochrome enzymes and drug transporters [ 12 ]. Chloroquine, hydroxychloroquine and azithromycin have also been proposed for the treatment of COVID-19, but they may intensify pharmacodynamic-related DDIs because the negative effects on the heart may exacerbate the cardiac toxicity of chronically administered drugs aimed at treating co-morbidities [ 13 – 15 ]. Additionally, patients hospitalized for COVID-19 may receive other drugs for the treatment of specific symptoms, further aggravating their overall pharmacological burden.…”

Clinical update onCOVID‐19 in pregnancy: A review article

“…50 Caution must also be exercised when considering its use for pregnant women with underlying mental health problems as HCQ may interact with antipsychotics, anti-depressants and methadone increasing the risk of QTc-prolongation, torsade de pointes (TdP) and potentially death. 51…”

Potential drug–drug interactions associated with drugs currently proposed for COVID‐19 treatment in patients receiving other treatments

“…The cessation of smoking, inherent to hospitalization, can also cause unexpected drug interactions. Only the drugs for which a proven risk of interaction exists will be presented below [66].…”