The cough medicine that parents love to buy has not been approved abroad due to insufficient evidence
"Industrial monosodium glutamate" in food, thickening, suspension, emulsification, stabilization, shape retention, film formation, puffing, freshness, acid resistance...
Important excipients of pharmaceuticals, indispensable disintegrants, excipients, stabilizers for various dosage forms such as capsules and tablets.
Prescription drugs that can "regulate children's immunity" for the treatment of bronchial asthma induced by recurrent respiratory tract infections in children.
The above three sentences describe the same "sodium carboxymethyl starch".
The earthy advertising slogan of "with carboxymethyl starch sodium, cough and asthma" seems to be no longer familiar, but in the current period of high incidence of respiratory infections, "carboxymethyl starch sodium solution" as a "prescription drug" on an Internet platform ranks second on the list of children's cough drugs.
Source: An Internet platform medicine list
When it comes to "sodium carboxymethyl starch", Lin Lin, the attending physician of a children's hospital in central China, feels both strange and familiar: "The hospital does not have this medicine, and I have not prescribed a prescription with sodium carboxymethyl starch solution for several years." Zhang Yinan, another pediatrician at a tertiary hospital in South China, even said that he did not know that this drug was available.
"Like many doctors' skepticism, I am not sure of its efficacy from the available evidence. And the so-called immune regulation, are there really so many children who need to be regulated?"
Excipients "anti-customer-oriented", is it a panacea or a placebo?
Sodium carboxymethyl starch, we also call it "sodium carboxymethyl starch", is actually an "upgraded version" of starch, which is obtained by replacing the hydroxyl group in the starch molecule with a carboxymethyl group through a chemical reaction. Its main use in the pharmaceutical industry is to make capsules, tablets of excipients, so that drugs can be better dispersed, dissolved, easier to absorb.
The food industry is another major use of sodium carboxymethyl starch, which has good emulsification dispersion and solid dispersion when dissolved in water, so that the oil particles are distributed more evenly, and it plays an improving role in bread and cake making.
Source: Online shopping platform
As a drug, the label shows that sodium carboxymethyl starch is "an immunomodulator, clinically used in children with recurrent respiratory infections and bronchial asthma induced by it."
Unlike Lin Lin's attitude, Zheng Feng, a pediatrician at a county hospital in South China, uses it in prescriptions, and he also introduced that in other hospitals and clinics he knows, doctors will prescribe sodium carboxymethyl starch: "The instructions clearly state that there should always be a certain medicinal effect." After all, it is a legal, national medicine quasi-word medicine."
Up to now, a total of 9 drugs with sodium carboxymethyl starch as the active ingredient have been approved, and 27 drugs have been filed in various places.
Source: State Food and Drug Administration
"For children with recurrent respiratory infections, we may recommend taking it for a period of time, usually 3 months."
In response to the question of carboxymethyl starch sodium, Zheng Feng also heard: "To ask me how much it helps children with recurrent (respiratory) infections, after all, it is all together with anti-infection and anti-allergy treatment, and the child's own immunity will also change, and it is difficult to say whether it can be attributed to this drug."
The question of sodium carboxymethyl starch has attracted high attention on the Internet a few years ago. Several pharmacists have publicly expressed their views that they are more placebos than adjuvant drugs, and even explicitly opposed their use in children.
Immunomodulators are immunosuppressants and immunoboosters. Over the years, there have been some sporadic studies in China, trying to prove that sodium carboxymethyl starch can enhance immunity.
In CNKI's 29 papers with the keywords of "carboxymethyl starch sodium" and "recurrent respiratory infections", more than two-thirds of the studies, carboxymethyl starch sodium was only used as part of the combination drug, and the remaining 9 studies failed to clarify how carboxymethyl starch sodium achieved the regulation of the immune system, and the study sample size was less than 150 cases.
Study sample sizes need to be estimated on a case-by-case basis, and we generally think that phase III clinical trials require hundreds to thousands of people to demonstrate drug efficacy.
On the safety side, according to the State Food and Drug Administration's "Guidelines for General Consideration of Drug Clinical Trials", for non-critical patients with long-term medication, the total sample size required to expose common adverse events is about 1500 cases (including short-term exposure). The first adverse event often occurs within the first few months, taking the clinical treatment period of 6 months as an example, about 300~600 cases are required to expose the common adverse event rate [1].
Looking back at the simple instructions of the drug, the mechanism of action, adverse reactions, and contraindications are not clear.
Source: China Medical Information Management Platform
A search of sodium carboxymethyl starch in PubMed did not find any immunomodulatory studies and clinical trial papers, all in the field of pharmaceutical excipients. Searching the clinical trials database, there were also no trials going on.
The Journal of Clinical Pediatrics once published a paper pointing out that recurrent respiratory infections in children are a clinical concept rather than a disease definition, and the connotation and extension are too broad, "not conducive to clinical research to analyze the cause, let alone clinical treatment, this clinical concept is rarely used in foreign related research, and is only mentioned as a symptom description in related disease research." [2]
As an indication, the concept of disease is vague and there is a lack of human clinical trial data, and sodium carboxymethyl starch solution has not been approved for marketing abroad so far and has become a drug.
Lin Lin's senior doctor Huang Enming also does not prescribe sodium carboxymethyl starch, but not just because he is worried that it is useless: "If anti-infection requires high immunity, but asthma is because of the high reactivity of the airways, the immunomodulators used for asthma are also inhibited, does it really make sense to use sodium carboxymethyl starch as an enhancer?"
"We need clear mechanisms, we need evidence of efficacy of monotherapy. There has been no evidence of sufficient grades of drugs that sell so well, did they not do research, or did they not produce results?"
Insufficient efficacy verification, should this drug still be used?
The Clinical Pathway for Recurrent Respiratory Infections in Children (2022 Edition) lists immunomodulators as the main type of prophylactic medication [3].
The guidelines do not mention the use of sodium carboxymethyl starch solution, but only describe the two drugs "bacterial lysate" and "pidotimod", pointing out that clinicians can refer to the clinical research data and application experience of such drugs, and choose appropriately according to different children's conditions, and specifically point out that "blind use of immunomodulators and preparations that are not fully clinically validated should be avoided."
Source: Literature 3
Pidotimod, which was popular like sodium carboxymethyl starch and used as a "panacea", was eventually banned in children under 3 years of age due to unclear efficacy and adverse reactions. Perhaps because it is not in the medical insurance catalog, the widely questioned sodium carboxymethyl starch has been used during the same period.
Immunomodulators are controversial, often not a necessary part of treatment in infectious diseases, but it is easy to arouse the sensitive nerves of the public in the epidemic of infectious diseases, and the efficacy and safety of drugs are unknown but are promoted as "miracle drugs" from time to time, while many countries have quite strict approval of immunomodulators.
Meiling Lin, Ph.D., of the University of Kansas, and Lianmei Ji, a former pharmacist at Beijing United Family Hospital, pointed out in an article: "In today's evidence-based medicine, it is not enough to rely solely on theory to explain the indications of a drug, but it is more necessary to support the evidence of human clinical trials with a realistic and sufficient sample size."
This paper also pointed out that there are hidden dangers in the use of sodium carboxymethyl starch. For example, children aged 1~4 years old take 7mL of sodium carboxymethyl starch solution with a sodium content of 22.5g/100mL three times a day, and the sodium intake has reached 400mg, accounting for half of the recommended daily sodium intake of children.
Children's kidney function is not yet mature, too much sodium salt will bring a certain burden to the kidneys, may lead to high blood pressure, and even further aggravate the situation of respiratory infections.
"Sodium carboxymethyl starch is not like a propylene ball, and many parents will be very persistent in chasing the doctor to prescribe it. According to my observations, it is not so well-known, and doctors can still lead." Huang Enming believes that the role of doctors is still important in the use of such non-medical insurance self-paid drugs.
"It is not recommended without evidence-based evidence, and even if serious adverse reactions do not occur, it cannot be used casually. Moreover, a bottle of medicine is 42 yuan, 3 months of thousands of dollars, and it is self-paid medicine, parents can not care about spending money for their children, but doctors can't directly ignore it."
Lin Lin said that the children's hospital where she works no longer has sodium carboxymethyl starch solution, and the drug has not entered the medical insurance, but after all, it is a legal drug or many doctors recognize: "In addition, "can regulate immunity" is too much gold oil, and it is too good to attract parents, and doctors should be willing to give the child's parents a comfort."
And the high sales of sodium carboxymethyl starch solution on the Internet also made Lin Lin a little helpless about her persistence.
"Even if I insist on it, it's really easy for parents to buy it on the online platform."
Acknowledgements: This article has been professionally reviewed by Ji Lianmei, Vice Chairman of the Pharmaceutical Service Innovation Committee of the Chinese Pharmacists Association, former pharmacist at Beijing United Family Hospital and director of the Pharmacy of United Family Rehabilitation Hospital
In the text, Lin Lin, Zhang Yinan, Huang Enming, and Zheng Feng are pseudonyms
Curated by: Yunye | Executive Producer: Gyouza
Source: Visual China
The author of this article: Yunye
Bibliography:
[1] https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/ggtg/qtggtg/20170120160701190.html
[2] SHEN Chaobin, JIANG Jinjin, CHEN Tongxin. Analysis of the implementation of guidelines for recurrent respiratory tract infections in children[J]. Journal of Clinical Pediatrics, 2016(11):842-845.
[3] Allergology Group, Pediatrician Branch of Chinese Medical Doctor Association, Respiratory Group of Pediatrician Branch of Chinese Medical Doctor Association, Rheumatology and Immunology Group of Pediatrician Branch of Chinese Medical Doctor Association, etc. Clinical diagnosis and treatment path of recurrent respiratory tract infection in children (2022 edition)[J]. Chinese Journal of Practical Pediatrics, 2022(037-003).