The National Health Surveillance Agency (Anvisa) determined, last Monday (27), the immediate suspension of medicines containing the clobutinal. In addition to manufacturing and use, the new measure affects import, distribution, marketing and advertising related to the product.
Present in cough syrupsafter the agency identifies risk of . According to the opinion of the agency’s pharmacovigilance area, the measure considers that the risks of the active ingredient outweigh the therapeutic benefits.
What is clobutinol and where was it found?
HAS CNN Brazilthe pulmonologist Michele Andreatafrom Saúde no Lar, explains that clobutinol is a substance with antitussive action, that is, used for , especially in cases of dry and irritating cough.
“It was mainly found in cough syrups and other medicines aimed at symptomatic relief of respiratory diseases. Its main effect is to act directly on the central nervous system, reducing the cough reflex without necessarily treating the underlying cause, which made it useful in specific situations, such as a persistent cough that interferes with sleep or quality of life”, he says.
According to the expert, the drug was considered effective precisely because it acts directly on the so-called cough center, located in the brain stem, reducing the excitability of the neurons responsible for triggering this reflex.
“This central mechanism allows the frequency and intensity of coughing to be reduced relatively quickly, which brings significant relief to the patient. Unlike other approaches that act on the periphery, such as in airway inflammation, clobutinol modulated the neurological response, which explains its more direct and noticeable action”, he comments.
Suspension of the drug in Brazil
As Michele explains, the withdrawal of clobutinol from the Brazilian market occurred after scientific evidence demonstrated that the substance can interfere with the electrical conduction of the heart, specifically prolonging the QT interval on the electrocardiogram, which increases the risk of potentially serious arrhythmias, such as torsades de pointes.
“This type of change can evolve into more serious cardiac events, including the risk of sudden death in rare cases. Although it is not a common effect in all users, it is an unpredictable and clinically relevant risk, which led regulatory bodies to consider that the potential harms outweigh the benefits”, he analyzes.
The measure, in fact, follows a movement already absorbed in other countries. In 2007, the European Medicines Agency began a review of the active ingredient after its removal in Germany.
At the time, clinical data associated the substance with QT interval prolongation, including in healthy patients. Given the information, the committee saw more risks than benefits, recommending withdrawal from commercialization throughout the European Union.
Manufacturer Boehringer Ingelheim voluntarily removed the products from the markets, contributing to the significant and global reduction of the substance.
A United Nations report cites the principle in a list of substances whose consumption or commercialization has been banned, withdrawn or severely restricted by governments around the world.
In the United States, to date, there has not been a publicly released decision formally announcing a ban, as in Brazil or Europe.
Cardiac risk associated with clobutinol
Given the suspension, the pulmonologist clarifies that the risk is not completely predictable and may occur even with short-term use, especially in individuals with greater susceptibility, such as those predisposed to changes in heart rhythm, electrolyte disorders or concomitant use of other medications that also prolong the QT interval.
“Still, factors such as high doses and prolonged use can increase this risk. The big challenge is that there is no simple way to identify in advance which patients will develop this complication, which reinforces the concern about the safety of the substance”, he details.
Medicines that offer the same effectiveness without the risks
Currently, there are other, safer therapeutic options for cough control, and the choice, as the professional points out, always depends on the cause of the symptom.
“Antitussives such as dextromethorphan, in addition to approaches that treat the origin of the cough, such as anti-inflammatories, bronchodilators or antihistamines, can be indicated on a more individualized basis”, he says.
“In many cases, the most appropriate approach is not just to suppress the cough, but to investigate and treat the triggering factor, following recommendations based on evidence and guidelines from medical societies, thus ensuring greater safety and effectiveness in patient care”, he concludes.
