Health warns of the danger of mixing hydroxychloroquine with other drugs

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The Spanish Agency for Medicines and Health Products (Aemps), under the Ministry of Health, published a note on Wednesday warning that it is not advisable to combine chloroquine or hydroxychloroquine with other medications that share the risk of prolonging the QT interval of the electrocardiogram (ECG), especially in patients with risk factors for a prolonged QT interval.

What exactly is the QT interval? It is a part of the electrocardiogram that indicates the time in which the heart recovers after a contraction, "which is when it is most vulnerable and it is easier for an arrhythmia to occur; the longer that time is prolonged the more risk of arrhythmia there is", explains Javier Jiménez Candil, president of the Heart Rate Association of the Spanish Society of Cardiology (SEC), who adds that QT interval prolongation is associated with ventricular arrhythmias that can be life-threatening , even ending in sudden death.

Remember that hydroxychloroquine (a medicine in use against malaria) is being used in combination with azithromycin (an antibiotic used among other things for pneumonia, for example) to treat Covid-19. The first can prolong the QT interval of the ECG in high doses; the second clearly prolongs it, so the combination of both drugs poses an even greater risk .

"The information note from the Aemps emphasizes and remarks in the final part that this combination of drugs is not recommended in patients at risk because it is being done in these circumstances of crisis by the coronavirus. Not so much hydroxychloroquine alone, which would be at high doses , but azithromycin does. The Aemps tries to avoid in general the combined use with other drugs and, eye, that we also look at other drugs that this patient may be taking chronically, "emphasizes Javier Jiménez Candil, who stresses that" Those of us who are dedicated to arrhythmias have been on notice for a long time. "

Jiménez Candil points out that there are two fundamental risk groups. "On the one hand, those who have genetic alterations in which the prolongation of the QT interval are already present. They are few and often identified. And, on the other hand, those with heart disease known as heart failure, or someone who has had a heart attack , and may have a tendency to this prolongation of the QT interval ".

The expert maintains that the first is "to identify these risk patients. The second is to assess the risk-benefit ratio in the use of hydroxychloroquine since its efficacy is not proven. And, third, to monitor the QT interval: in in the case of patients at risk before and after administering the drug to decide whether to continue or not, and in the case of non-risk patients, after a day of treatment. In both cases, if the drug is maintained, it is necessary to measure it frequently to see the additive character (sum of the effect of each drug) ".

For Jiménez Candil, the Aemps document emphasizes avoiding such joint use, not only in patients with Covid-19, but also those with rheumatoid arthritis, for example, who are also administered hydroxychloroquine to decrease inflammation; and "in being aware of the drugs that a patient is already taking that added to hydroxychloroquine can enhance QT prolongation, such as some commonly used antibiotics, such as erythromycin, or medications such as haloperidol, for example, indicated for older people with psychomotor agitation.

On this risk of prolongation of the QT interval in patients with Covid-19, the Aemps collects in its note a recent study published on April 10 in MedRxiv , although it is a repository of the University of Yale and British Medical Journal that collects preprints , that is, studies that have not been peer reviewed or published in scientific journals. That preprint concludes that "short-term treatment with hydroxychloroquine is safe, but the addition of azithromycin may induce heart failure and cardiovascular mortality , possibly due to synergistic effects on QT interval length. We call for caution if such a combination is going to use in managing the Covid-19 ".

Apart from this preprint , the Aemps recalls that "currently, no randomized controlled clinical trial has demonstrated the efficacy of these drugs for the treatment of patients with Covid-19. To date, the information available on their antiviral action comes from studies in In vitro and series of patients with limitations in size and methodology Different studies are being carried out ( only in Spain there are 11 authorized clinical trials ) to evaluate its efficacy and safety against SARS-CoV-2 "and that" chloroquine and hydroxychloroquine they also have other potential risks, including hypoglycemia, digestive disorders, and neuropsychiatric disorders. "

The medicine of discord

Hydroxychloroquine has become famous in this crisis for its experimental use in several Chinese hospitals in full swing, but above all for a study by the eminent French virologist Didier Raoult, who divulged to the four winds the benefits of hydroxychloroquine combined precisely with azithromycin. to treat the coronavirus. The downside is that the study he conducted at the University Hospital Institute (IHU) in Marseille, a reference center for infectious diseases that he directs, collects a very small sample of just 42 patients affected by SARS-CoV-2 , in addition of other limitations such as a non-randomized design or one that did not include a parallel group to the one given placebo.

Although the President of the United States, Donald Trump, was one of the defenders of this medicine at first - against the recommendations of his own scientific team -, the truth is that, as a result of the study by Didier Raoult, others who question the effectiveness of hydroxychloroquine and the medical community are divided over its benefits in treating Covid-19, at least in an advanced stage. In this sense, the researcher Oriol Mitjá is conducting a study in Spain, led by the Foundation to Fight AIDS and Infectious Diseases, which aims to measure the efficacy of the drug in the early stages of Covid-19 and to prevent the disease in people. not infected, something that would be very useful for healthcare personnel.

Just in case, various countries have included hydroxychloroquine as a treatment alternative to treat the coronavirus and due to the boom , Health imposed some restrictions on the marketing of the drug, such as controlled distribution and control of the stock available through the Aemps, prioritizing the treatment of chronic patients of other diseases that take it, and the use in clinical trials and therapy of patients admitted with pneumonia.

According to the criteria of The Trust Project

• Science and health
• Coronavirus
• Covid 19
• Infectious diseases
• Respiratory diseases

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