What does it mean that the domestic anti-COVID-19 drug was taken off the shelves within one day of its launch?

It came with the halo of "the first domestically produced oral new crown drug", but it was removed from the shelves of an online pharmacy within just one day of opening for retail sales... With the recurrence of the epidemic, the azithromycin tablets brought by Real Bio (Henan Real Biotechnology Co., Ltd.) have occupied the headlines many times in the past six months. The "removal storm" this time also reflects the anxiety of people about self-protection in the new stage of anti-epidemic efforts.

Image source: Weibo screenshot

According to the announcement released by Real Biology, the Azvudine tablets sold in the online pharmacy are "anti-HIV-1 indication drugs" [1]. This is the original indication for which the drug was approved - in July last year, the National Medical Products Administration conditionally approved the marketing of Azvudine tablets for use in combination with nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors to treat adult HIV-1 infected patients with high viral loads [2].

One of the reasons why the online retail of Azvudine tablets caused such a big stir is that the drug should not be so easily available to ordinary people .

According to the “Notice on Including Azvudine Tablets in the Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia,” patients should use the drug under the guidance of a physician, and physicians not only need to have a deep understanding of the drug’s adverse reactions and drug interactions, but also need to avoid using it in patients with contraindications [3]. It can be seen that it is not a drug that ordinary people can stockpile at home and take according to their own understanding, like regular cold medicine tablets.

In fact, if used improperly, the drug may also cause serious side effects .

According to the Azvudine Tablets Instructions, the drug may cause symptoms of the nervous system and gastrointestinal system , and may also cause abnormalities in liver function, kidney function, and hematological parameters . Animal studies have also shown that the drug has certain reproductive toxicity , which may cause a decrease in ovarian and uterine weight, or cause embryo and fetal developmental toxicity.

Based on these research results, even if it is included in the diagnosis and treatment plan for COVID-19, the drug is “not recommended for use during pregnancy and lactation, and should be used with caution in patients with moderate to severe liver or kidney damage.”[4]

One might ask, if azithromycin causes such serious side effects, why was it approved in the first place?

As the saying goes, "All medicines are poisonous". Most drugs will cause adverse reactions while treating diseases. When approving a drug for marketing, experts will comprehensively consider its efficacy and adverse reactions and conduct a more comprehensive evaluation. In professional terms, it is to evaluate the "risk-benefit ratio" of the drug. After balancing the two, a drug's marketing application will be finally approved or rejected.

The significance of azithromycin tablets becomes apparent when the patient’s life is seriously threatened by COVID-19. When reviewing the development history of azithromycin tablets this year, Professor Jiang Jiandong, an academician of the Chinese Academy of Engineering and dean of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, said that the drug “can significantly shorten the time it takes for moderate COVID-19 patients to improve their symptoms, increase the proportion of patients with improved clinical symptoms, and achieve clinically superior results” and that “azithromycin is more effective in patients with severe cases who have a higher viral load.”[5]

In other words, Azvudine can have a better effect on patients with moderate or severe symptoms . However, in this new stage of fighting the epidemic, the vast majority of COVID-19 patients do not develop severe symptoms.

According to the latest news on the official website of the National Health Commission, as of 24:00 on November 19, there were 20,829 confirmed cases, including 95 severe cases[6]. In other words, among all confirmed COVID-19 patients, the proportion of severe cases is less than 0.5%. If we consider that there are 189,669 asymptomatic infected people who are still under medical observation, the overall proportion of severe cases is less than 0.05%. This is why it is not recommended for ordinary people to stock up on this medicine - the probability of needing it is too low. Even if you need to use it, you must follow the doctor's instructions[7].

As mentioned at the beginning, the attention that Azvudine has received under the current new situation reflects the public's emphasis on self-protection and the anxiety it has caused. Obviously, no one wants to get sick. If unfortunately infected, I believe everyone also hopes that their symptoms are as mild as possible, preferably no symptoms.

Although Azvudine Tablets have been approved for the treatment of COVID-19, its use has very clear limitations and is not a panacea for the prevention and treatment of COVID-19 . For ordinary people, the most recommended method by public health experts is the COVID-19 vaccine . It can mobilize the body's own immunity, not only to reduce the risk of infection from the source, but also to reduce the risk of severe illness after unfortunately being infected with the new coronavirus, killing two birds with one stone. With the arrival of autumn and winter, non-drug measures such as wearing masks, washing hands frequently, reducing crowds, and maintaining social distance will also play an important role in further reducing the risk of COVID-19.

References:

[1] Henan Real Biotechnology Co., Ltd. released a statement [EB/OL]. Real Biotechnology. 2022-11-19.

[2] The National Medical Products Administration conditionally approved the registration application of Henan Zhenzheng Biotechnology Co., Ltd. for the addition of the indication of COVID-19 treatment for Azvudine Tablets [EB/OL]. 2022-07-25. https://www.nmpa.gov.cn/yaopin/ypjgdt/20220725165620176.html

[3] Notice on the inclusion of azithromycin tablets in the diagnosis and treatment plan for novel coronavirus pneumonia [EB/OL]. Medical Administration Bureau. 2022-08-09. http://www.nhc.gov.cn/yzygj/s7653p/202208/33e3ff4308b4446796c3f315601d436f.shtml

[4] Azvudine tablets instructions [DB/OL]. https://file.wuxuwang.com/zhuce/ssypfiles/78da81a9010d86837acf314780c4798c%E8%AF%B4%E6%98%8E%E4%B9%A6.pdf

[5] Wang Zhenya. 931 days and nights! The story behind the development of the first domestic oral anti-COVID-19 drug [EB/OL]. Health Times. 2022-08-07. https://www.imb.com.cn/xwdt/b10f79b2795d4336886850af2eb340d8.htm

[6] The latest situation of the novel coronavirus pneumonia epidemic as of 24:00 on November 19 [EB/OL]. National Health Commission. 2022-11-20. http://www.nhc.gov.cn/xcs/yqtb/202211/7c1dec0a19cd49b9a11102606cf00657.shtml

[7] Sun Hongli. Domestic oral COVID-19 drug Azvudine tablets included in diagnosis and treatment plan [EB/OL]. People's Daily Online. 2022-08-10. http://health.people.com.cn/n1/2022/0810/c14739-32498886.html

Author: Ye Shi

Review | Jin Dong, Associate Researcher, Institute of Infectious Diseases, Chinese Center for Disease Control and Prevention