RIO DE JANEIRO, BRAZIL – Brazilian pharmacies sold over 52 million tablets of four drugs from the so-called “covid kit” in one year of pandemic: hydroxychloroquine sulfate, azithromycin, ivermectin, and nitazoxanide. According to an exclusive survey by Agência Pública, more than 6.6 million bottles and boxes of these four drugs were sold from March 2020 to March 2021.
Within all this demand of custom boxes and packaging boxes have increased.
The figures represent only the sales of these drugs in private pharmacies, i.e., they do not include what was given in hospitals or dispensed in clinics of the National Health System (SUS).
According to Pública’s survey, among the four drugs, the one with the most pills sold was hydroxychloroquine – which President Bolsonaro announced he was taking when he was diagnosed with Covid-19. There were more than 32 million pills sold since March 2020, a total of 1.3 million boxes.
Since the end of March 2020, hydroxychloroquine joined the list of special control drugs, along with chloroquine, by decision of the Brazilian Health Regulatory Agency (ANVISA). It was this change in classification that made it possible to account for the sale of hydroxychloroquine in this base of substances.
ANVISA itself acknowledged that the inclusion of the drugs in the category was intended to “curb the indiscriminate purchase of drugs” due to the pandemic, although it had alerted at the time that “there are no conclusive studies on the use of these drugs for the treatment of Covid-19.” The package insert for hydroxychloroquine provides for it to be used to treat malaria or certain autoimmune diseases, such as lupus and rheumatoid arthritis.
Second placed in sales, azithromycin, an antibiotic, had over 13 million tablets sold in Brazilian pharmacies in the same period – more than 3 million boxes. Unlike hydroxychloroquine, azithromycin had been included in the group of drugs under special control at least since 2010, when ANVISA defined a rule for antibiotic control. The sale of azithromycin in Brazilian pharmacies increased from an average of 711,000 tablets a month in 2019 to 1 million a month during the pandemic. The intended use of azithromycin in package inserts is
Both hydroxychloroquine and azithromycin had their peak sales in March 2021, the month with the most Covid-19 deaths since the pandemic began. March was also the month with the most deaths recor for the treatment of diseases such as bronchitis, pneumonia, sinusitis, and pharyngitis.ded in the country’s history, according to civil registry offices.
Ivermectin and nitazoxanide, two anthelmintics (anti-worm medicines), were not included in the category of special control drugs throughout the pandemic – that is, the data record only a part of the sale of these drugs in Brazilian pharmacies. Nitazoxanide joined the special control group in April and ivermectin in July. Then, in August, President Bolsonaro stated on his social networks that ANVISA would facilitate access to hydroxychloroquine and ivermectin and that the population could buy the drugs “with a simple prescription.”
In September, ivermectin and nitazoxanide were excluded from ANVISA’s special control classification, thereby enabling the prescription to be reused and more drugs to be purchased without the need for a new prescription. During the period in which the two drugs were under special control, peak sales of ivermectin occurred in August 2020. The peak for nitazoxanide occurred in July.
Sought by Pública, ANVISA replied that “it is not possible to issue considerations about any data or specific information” regarding the sales data of the drugs found by the report.
The state of Goiás bought more boxes of the four covid kit drugs in relation to its population. It is also there where the most boxes of azithromycin were sold proportionally. The Federal District, on the other hand, was where more hydroxychloroquine and ivermectin were sold in relation to the population, and Amapá where nitazoxanide sales were higher proportionally.
In turn, São Paulo tops the states where the four covid kit drugs were most sold in absolute numbers – about 1.5 million boxes, more than a fifth of the total sold in Brazilian pharmacies in the pandemic.
“There is no doubt that off-label use (outside the purpose of the package insert) is responsible for the large sales of these and other drugs from the ‘covid kit’, which are often placed in strategic places on pharmacy counters to attract customers’ attention,” says Adriano Andricopulo, researcher at the Institute of Physics of São Carlos at USP and expert in medicinal chemistry.
“The increase in sales is associated with people’s expectation, which unfortunately is still high, of obtaining the possible therapeutic benefits and protecting themselves against the disease. But these drugs simply don’t work: the ‘kit’ is useless,” he says.
The use of drugs from the “covid kit” was publicly advocated and encouraged by President Jair Bolsonaro for the “early treatment” of Covid-19, despite being advised against or refuted by national and international health and research bodies. According to a March 2021 World Health Organization (W.H.O.) protocol, hydroxychloroquine is not recommended for Covid-19 patients irrespective of the severity of the disease; and ivermectin is contraindicated except in clinical trials.
In Brazil, directors of health regulator ANVISA have stated that there are no drugs to prevent or treat the disease early; the Brazilian Society of Infectology (SBI) does not recommend the treatment, and the Brazilian Medical Association (AMB) has published that the four drugs in the kit have no proven scientific efficacy and should be banned for the treatment of Covid-19.
The Federal Council of Medicine, however, says it neither supports nor condemns early treatment and argues that individual doctors can define the best treatment for patients.
Records of adverse effects of “covid kit” drugs have increased in the pandemic
With millions of pills sold, the records of adverse effects caused by the administration of kit drugs have increased in Brazil. Since April last year, ANVISA has received 456 notifications of adverse effects on the use of the four “covid kit” medicines. The amount is ten times higher than in the same previous period, from April 2019 to April 2020.
Of the notifications during the pandemic, 173 were serious. The most common reported effects are cardiovascular symptoms -such as disturbances in heartbeat rate-, liver damage, diarrhea, and nausea.
According to Ana Paula Herrmann, a pharmacology researcher at the Federal University of Rio Grande do Sul, every drug has adverse effects, although many times the benefits for its indication outweigh the risks. According to her, this does not occur with the covid kit. “The problem is that in the absence of benefits, all that’s left are risks. And then there is nothing to justify its use, because the risks can often be unpredictable.”
Herrmann comments that adverse effects such as arrhythmia and kidney damage caused by the combination of hydroxychloroquine and azithromycin are expected, but others are unknown because until now, these drugs were restricted to a certain group of patients, and were not used by a large part of the population.
The companies selling the “covid kit” in Brazil
In Brazil, 23 companies hold the registration for the four drugs in the “covid kit” that were sold in pharmacies: hydroxychloroquine sulfate, azithromycin, ivermectin, and nitazoxanide. Among them, EMS, from the NC Group, is the only one to produce all four drugs. The president of the group, Carlos Sanchez, is listed as one of the 30 billionaires in the country in Forbes Magazine’s survey and, according to the report, was present at the dinner where Bolsonaro met with entrepreneurs on April 7th in São Paulo.
EMS was granted ANVISA approval to conduct a clinical trial with hydroxychloroquine in patients with Covid-19. Besides EMS, the NC Group also owns Germed, which produces hydroxychloroquine sulfate, azithromycin, and nitazoxanide.
Sought by the report, EMS said it “advises that the drugs ivermectin, hydroxychloroquine, azithromycin and nitazoxanide be used according to the indications in their respective package inserts, under medical prescription” and that “these professionals are the only ones qualified to prescribe the proper use of these drugs, following the medical protocols.” Germed replied that “azithromycin, ivermectin, and nitazoxanide should be used as indicated in their respective package inserts and always under medical prescription.”
According to the Globo report, Renato Spallicci, Apsen’s CEO, which produces Reuquinol (commercial form of hydroxychloroquine), was received at the Ministry of Health before the government published the protocol that guided the use of the drug in mild cases of Covid-19.
Sought by the report, Apsen said it “has produced hydroxychloroquine sulfate in Brazil for 18 years, focusing on the treatment of chronic patients with lupus and rheumatoid arthritis and recommends its use only in the indications provided in the package insert, which are approved by ANVISA.” The company reinforced that “there is no approval by any health regulatory agency, neither by the WHO, for its use in the treatment of Covid-19.”
Sanofi Medley is the only foreign company authorized to commercialize hydroxychloroquine in the country. The French pharmaceutical company has former U.S. President Donald Trump as a shareholder, who advocated the drug in the fight against coronavirus.
In a statement to the report, the company said that “today, Sanofi’s hydroxychloroquine-based drugs (Plaquinol) are officially registered in more than 60 countries for use in some dermatological and rheumatological diseases, as well as for malaria and lupus, in some countries such as Brazil. Currently, the approved indications for Plaquinol do not include treatment or prevention of Covid-19 anywhere in the world.”
Source: El Pais