What "cold" medicine causes infertility in men? There are plenty of similar questions and reviews on the Internet. What is the reason for fears that Kagocel affects male fertility? For example, there is an opinion that gossypol, a cotton pigment and the active component of kagocel, reduces the chances of conception in men. Is it really?
It is believed that antiviral drugs such as Kagocel, which contains gossypol, a substance secreted from the vegetative parts of cotton, can suppress spermatogenesis and in some cases act as a male contraceptive. By its chemical nature, gossypol is a toxic alkaloid necessary for the plant to protect itself from harmful insect pests.
It is known that gossypol reduces the motility of mature sperm and leads to inhibition of developing forms of sperm, especially at the spermatid stage. It is also capable of inhibiting a number of proteins and enzymes contained in sperm and spermatogenic epithelial cells. It turns out that Kagocel can also cause infertility?
Kagocel: composition and dosage form of the drug
The active component of the medicine is a sodium salt based on carmoxymethylcellulose and a polyphenol compound of plant origin. Kagocel stimulates the formation of human interferons, immune proteins that suppress harmful microflora:
- macrophages;
- lymphocytes;
- endothelial cells;
- granulocytes;
- fibroblasts.
The drug has antimicrobial, immunomodulatory, radioprotective effects. Active against pathogens of ARVI and herpes simplex.
Kagocel is available in the form of tablets for oral use: biconvex, light brown in color with small inclusions. Packaging: contour blisters with 10 cells.
The drug tablet contains 12 mg of gossypol copolymer and auxiliary components:
- starch;
- calcium salts;
- lactose;
- povidone.
Mechanism of action
After administration, the active substance is concentrated mainly in the tissues of the liver, lungs, spleen, and kidneys during the day. A small amount accumulates in muscles, brain and blood plasma.
The protective level of interferons grows in the body over 48 hours and lasts up to 5 days from the moment of taking the medicine. This property makes it necessary to prescribe Kagocel at an early stage of the disease - no later than 4 days from the moment of infection.
It is excreted from the body through the intestines. It is not deposited in tissues, has no toxic effect, and does not cause cell mutations.
Chemical scientists: If Kagocel is safe, it means it is useless as a medicine
We remind you that at the end of January, State Duma deputy Sergei Shargunov sent an official request to the Minister of Health Mikhail Murashko to find out whether the antiviral drug Kagocel had undergone the necessary clinical trials. The deputy also asked how accurate is the information in the media that one of the side effects of Kagocel is infertility. Following this, comments appeared in the media, first from Roszdravnadzor, and with it - and (), as well as the Ministry of Health, claiming that clinical studies of the drug were carried out, there was no data on the risks associated with its use.
However, scientists have not believed in a drug with a complex active substance for a long time. Therefore, the RAS Commission for Combating Pseudoscience turned to the Russian University of Chemical Technology. Mendeleev with a request to clarify what the drug “Kagocel” is: “In the media, primarily on television, there is a large-scale advertising campaign for a drug for the treatment of influenza and ARVI called “Kagocel”. The composition of the active substance of the drug declared by the manufacturer causes serious confusion, and therefore I ask you to give professional advice on the issues that have arisen:
1. Sodium salt of a copolymer of (1→4)-6-0-carboxymethyl-β-D-glucose, (1→4)-β-D-glucose and (21→24)-2,3,14,15,21 ,24,29,32-octahydroxy-23-(carboxymethoxymethyl)-7,10-dimethyl-4,13-di(2-propyl)-19,22,26,30,31-pentaoxaheptacyclo [23.3.2.216.20.05. 08.28.27.09.18.012.17] dotriaconta-1,3,5(28),6,8(27),9(18),10,12(17),13,15-decaene - this is the chemical name, chemical formula or something else?
2. Could a substance with a similar chemical name or chemical formula exist in principle?”
The Chairman of the RAS Commission on Combating Pseudoscience, Academician of the Russian Academy of Sciences Evgeniy Aleksandrov received a response from Anna Shcherbina, Vice-Rector for Science of the Russian University of Chemical Technology. Mendeleev, which explains the origin of such a complex name. It was obtained by a chemical substance formed by the interaction of carboxymethylcellulose with gossypol, from the authors of the Russian Federation patent No. 2270708 (“Sodium salt of a copolymer of carboxymethylcellulose and gossypol, pharmaceutical composition and method for the prevention or treatment of viral diseases”).
As the chemists explain, “gossypol, a brown solid, is a phytoalexin polyphenolic compound found in the seeds, roots and leaves of the cotton plant. Gossypol is a biologically active compound. It exhibits antiviral and antimalarial activity.” Its side effects include suppression of spermatogenesis and hepatotoxicity, “which prevent its use as a medicine.”
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In the official response of the Russian Chemical-Technological University. Mendeleev scientists draw attention to the fact that in the polymer molecule “Kagocel” “gossypol is in a form associated with carboxymethylcellulose by covalent bonds and, in accordance with this, the structural element of gossypol cannot exhibit the biological activity inherent in the individual compound . In gossypol, we recall, it is antiviral and contraceptive, as well as toxic. However, in the human body this bound substance decomposes into its components, that is, the same “pure” gossypol is released - contraceptive and toxic. Scientists reassure: “the decomposition of this polymer compound with a molecular weight of more than 100,000 Da (Da - atomic mass units for measuring atoms and molecules - Ed.) in biological media with the formation of toxic gossypol is quite slow, as a result of which its concentrations in the human body are at oral use in accordance with the instructions cannot reach values hazardous to health.”
The RAS Commission for Combating Pseudoscience still has questions for the experts of the Russian University of Chemical Technology. Mendeleev. As Sergei Finaev, advisor to the chairman of the commission, said, scientists are going to send another request to the university, since they have not seen a specific answer to the question of what is the “sodium salt of a copolymer of carboxymethylcellulose and gossypol, indicated by a complex formula, a pharmaceutical composition and a method for the prevention or treatment of viral diseases.” : “Apparently, this is a polymer,” says Sergei Finaev, “which means it tends to accumulate in the body. Who studied this process and how remains to be seen.” It is clear that chemists will not be able to perform pharmacokinetic studies, which are usually carried out during preclinical studies of a drug. But they can tell whether Kagocel is actually excreted from the body unchanged (and therefore does no harm or benefit) or whether it accumulates and decomposes “with the formation of toxic gossypol quite slowly.”
Chief pharmacologist of St. Petersburg: We treat ARVI with the contraceptive “Kagocel” and the useless “Arbidol”
We remind you that Kagocel is an officially registered drug in Russia. This means that before allowing a drug onto the market, the Ministry of Health, in accordance with Russian legislation, conducted an examination of data from preclinical and clinical trials confirming its quality, effectiveness and safety .
As “Doctor Peter” said earlier, “Kagocel” - today an immunostimulating drug “for the treatment of ARVI” until recently had a completely different purpose: “it was used for a long time as a contraceptive drug, causing a disorder of spermatogenesis, and then suddenly it became an immunomodulator. In the late 1990s, a WHO study group on methods of regulating male fertility concluded that the risks of its use outweighed the benefits and its use in its pure form as a contraceptive was prohibited. Simply put, the use of gossypol, and now Kagocel, led to male infertility.”
© DoctorPeter
How to take Kagocel
The tablets are taken orally without chewing or breaking into pieces. Drink plenty of water. Meal times don't matter. Gastric juice does not affect the absorption of the drug into the bloodstream.
For prevention, adults and adolescents over 12 years of age are recommended to use Kagocel in cycles:
- 2 tablets each once within 2 days;
- repeated 2-day intake after a break of 5 days.
This scheme contributes to the formation and maintenance of the body’s defenses for a week after the next use of the medicine.
For the treatment of ARVI, the following is prescribed:
- 2 pills three times a day for the first 2 days;
- 1 pill three times a day on days 3–4.
A total of 18 tablets are enough for a 4-day course. Longer treatment is irrational.
When treating herpes, Kagocel is taken for 5 days: 2 pills three times a day. The course is designed for 30 tablets.
How to take Kagocel for children
Children 3–6 years old with the flu are prescribed:
- 1 pill twice a day for the first 2 days;
- on days 3 and 4 - 1 pill once.
Children 6–12 years old can take:
- three times a day, 1 pill in the first 2 days;
- in the remaining 2 days - 1 pill twice a day.
To prevent diseases in childhood, 2 tablets are enough for 7 days: 1 pc. daily for the first 2 days, then at a 5-day interval. Preventive treatment can be repeated throughout the epidemic season.
What is your evidence?
A child sick with the flu.
Photo: Vladimir Smirnov/TASS Kagocel's research consists mostly of in vitro studies, studies in animal models and observational studies. Only a few of these are clinical trials, and none of the age cohorts have undergone three-phase trials in large samples.
In the study “Clinical efficacy of Kagocel in ARVI with stenosing laryngotracheitis in children,” the sample included only 60 children aged 6 to 13 years (29 in the Kagocel group), which is acceptable for stage I clinical trials.
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If the result is positive, it should be followed by larger phase II and III samples. However, since no subsequent trials were conducted, the conclusion about effectiveness seems premature, especially since, in accordance with the results obtained, the difference in the duration of symptoms of ARVI and laryngotracheitis between the Kagocel group and the placebo group was no more than a day.
If we take into account that only 29 children took the drug, then a final conclusion about the safety of the drug after testing on such a small sample cannot be made, since it is impossible to trace even those side effects that occur with a frequency of 1:100, not to mention the more rare ones. .
The situation is similar with the study “Clinical effectiveness of the drug “Kagocel” for influenza and ARVI in children from 2 to 6 years old.” The drug was also studied in a cohort of only 60 children. There are also no follow-up tests for this age group.
There is another study by the same authors in 2012 on the same modest sample and their same work for the age group from 6 years on a sample of 120 participants (2009) to assess the preventive effectiveness of Kagocel, which is also not a valid sample for final conclusions about the effectiveness and safety in accordance with international standards.
Two clinical trials were conducted on adult cohorts: “The therapeutic effectiveness of Kagocel in the treatment of patients with uncomplicated influenza and influenza complicated by sore throat” and “The use of the drug Kagocel for the treatment and prevention of influenza and other acute respiratory viral infections” (not publicly available) .
The first is on a sample of 264 people, the second is on a sample of 331 people. This is the only Kagocel study carried out on a sample that meets the standards, however, it is also a single-stage one, and in addition, it evaluates the effectiveness not in treatment, but in prevention.
Production of the antiviral drug "Kagocel". Photo: Valery Melnikov / RIA Novosti
Thus, even if there were no further complaints about the design of the studies, their extreme smallness (especially for children) already makes them not meet international standards for this type of scientific work.
There is, however, another very serious limitation. The studies are single-blind, not double-blind, which does not guarantee objectivity and does not in any way correspond to international standards.
And finally, as noted above, according to the research results, the difference in the duration of symptoms, at best, was about one day - this is a rather modest result for a particular patient, taking into account the fact that he pays for this drug, which is not at all cheap, usually from your pocket.
There is one more very important circumstance. Influenza and ARVI are self-limiting infections, that is, they have a limited duration and in the vast majority of cases resolve without intervention (excluding complications).
In this situation, the requirements for evidence of effectiveness are particularly stringent. We must be sure that the disease did not go away on its own, but as a result of the study therapy, and in the case of Kagocel we do not observe compliance with even the basic rules.
So, the effectiveness of Kagocel, alas, has not been proven.
It is possible that someday he will conduct clinical trials according to all the rules and prove to us the usefulness of his product, but for now, sales success is based on skillful marketing, and not on solid scientific data.
What about security?
Is it possible to combine Kagocel with alcohol?
There is no data on the interaction of the drug components with ethanol and the formation of toxic compounds when used together. However, under the influence of alcohol, the mechanism of interferon formation may be disrupted. In such cases, the therapeutic effect of Kagocel will be insufficient or will disappear.
In addition, alcohol may increase the risk of allergic reactions and side effects while taking the medication. For these reasons, you should abstain from alcohol for a period of at least 5 days from the last time you took Kagocel.
How to check effectiveness
Photo: PA Images/TASS
In the modern world, the presence of studies in which a drug has demonstrated a therapeutic or preventive effect in one way or another is not yet a reason to declare it effective.
Typically, a drug candidate goes through several stages.
Its effect is studied in vitro: scientists observe how a potential therapeutic agent interacts with living cells of the body and with pathogens. Once convinced that it has therapeutic potential, it is tested on laboratory animals.
If a drug candidate does not cause serious adverse reactions in animals, it is tested in humans.
Typically, scientists first observe the effects of a drug in small groups of people, and then carefully design and conduct clinical trials according to very strict rules. Let's talk about the most important ones.
Firstly, such studies are carried out in three stages.
Phase I and II clinical trials may be conducted on a small sample of participants. As for phase III trials, they should be:
a) multicenter (which means research centers in different countries);
b) be carried out on a large number of participants (thousands) in order to minimize possible statistical errors in determining the effectiveness of the drug, as well as to establish all possible, including relatively rare, for example, 1:1000, unwanted side effects.
Such requirements are imposed on clinical trials by certifying agencies in all developed countries. They take the standards of the FDA and the US Food and Drug Administration as a model.
Secondly, clinical trials must have a control group.
This means that comparable numbers of participants take the drug candidate and the placebo (dummy). This allows you to separate the real effect of the drug from random improvements.
In this case, the groups must be randomized, that is, approximately the same in various parameters. You can't have one group dominated by men, another by women, one by people aged 20 to 30, another by people aged 40 to 50, one by rich people and another by people with low incomes.
Finally, clinical trials must be double-blind studies. This means that neither the patients themselves nor the doctors assessing the participant's condition at various stages of his treatment should know whether they are dealing with a real agent or a placebo.
This is absolutely necessary so that the results are not influenced by the “human factor”.
Only after passing all three phases of double-blind randomized controlled trials can a drug qualify for approval by the FDA or the relevant European agencies.
No pharmaceutical company can claim the effectiveness of their drug unless it meets the very strict modern standard outlined above.
