The onset of cold weather is traditionally marked by a surge in morbidity, including rotavirus infection. This disease, better known as intestinal flu, affects all people of all ages, but children suffer especially hard from it. According to WHO, of the total number of cases, 60-70% are small patients, and the overwhelming majority are of young age. Therefore, the search for adequate drugs to treat rotavirus is very urgent. First of all, attention is paid to drugs with antiviral effects - such as Kagocel.
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.
IFN - interferon
HPLC - high performance liquid chromatography
It is widely known that difficulties in the prevention and treatment of acute respiratory viral infections and influenza are associated with a large number (more than 200) of viral agents that cause respiratory diseases. Specific prevention of influenza has limited possibilities due to the high individual variability of the influenza virus. Every doctor is faced with the problem of choosing a drug for ARVI and influenza [1]. The criteria for choosing drugs of this type are universality of action, a possible combination of antiviral and immunomodulatory effects, the absence of viral resistance to the drug, oral administration, a minimum of side effects and affordability. Back in the second half of the last century, the universality of action for antiviral drugs that are interferon inducers (IFN) was established.
As is known, the IFN system is part of the immune system responsible for the body’s antiviral defense [2–4]. IFN inducers have a wide range of antiviral activity (etiotropic effect) and provide a pronounced immunomodulatory effect. The synthesis of endogenous IFN is balanced and controlled by the body, preventing side effects characteristic of exogenously administered IFN. Most viruses do not develop resistance to endogenous IFNs. As a result of many years of targeted screening, domestic virologists managed to create a group of original inducers that have a high therapeutic index and are suitable for both the prevention and treatment of a number of viral infections. Among such drugs is the domestic drug Kagocel [5]. After its single use, a longer circulation of IFN in the blood (120 hours) was observed compared to other drugs of this type [6]. When taken orally, the maximum production of IFN (α/β) is observed after 4 hours, and they circulate in the bloodstream for 4-5 days. The founder of the school for the development of new domestic inductors IFN, academician of the Russian Academy of Medical Sciences F.I. Ershov notes that Kagocel is one of the most studied antiviral drugs [5]. It causes the body to produce “late” IFNs, which are a mixture of IFNs (α/β), and also stimulates the production of physiological amounts of IFN-γ. The indisputable advantage of Kagocel is its proven effectiveness against various pathogens of viral infection. Thus, it has been found that it is effective against influenza viruses H1N1, H5N1, A (H1N1)v, A (H1N1), H5N1, acute respiratory disease SARS, herpes simplex type 2 (HSV type 2) [6-8 ].
The results of most scientific studies devoted to Kagocel are well presented to a wide practicing medical audience. These works deal primarily with studies on the clinical effectiveness of the drug. It is noteworthy that the proportion of publications devoted to its safety is not so large, since the works available in this regard are often published in highly specialized publications or in journals of experimental medicine.
The purpose of this review is to provide data on the safety of Kagocel to a wide range of practitioners.
Kagocel is an antiviral drug created on the basis of a polymer of oxidized cellulose with grafted chemically modified molecules of natural polyphenol - gossypol. The latter is a substance contained in cotton that protects the plant from various unfavorable factors. The natural polyphenol gossypol was discovered more than 100 years ago and immediately became the subject of scientific interest among scientists around the world due to a number of its unique properties. As a result of numerous scientific studies, it has been established that it has a pronounced pharmacological effect, exhibiting antiviral, antioxidant and immunomodulatory activity [9]. Foreign researchers have identified the antitumor and antimetastatic properties of gossypol [10, 11]. However, it should be noted that the use of gossypol as a drug is limited by its small therapeutic breadth in terms of the doses used, especially when administered systemically. The results of numerous studies have shown that this natural polyphenol is toxic in its free form. It has a negative effect on erythro- and myelopoiesis and exhibits hepatotoxicity; causes DNA breaks in lymphocytes, Sertoli cells; has embryotoxic properties [12, 13]. It is known that gossypol can inhibit spermatogenesis [13]. In this regard, at the end of the last century, foreign pharmacologists attempted to create a new contraceptive based on gossypol. However, during clinical trials, it was concluded that further research in this area was inappropriate due to the inconsistency of the results with the requirements of the risk-benefit ratio [14]. Gossypol can have a negative impact not only on the male reproductive system. It has been established that it causes inhibition of the ovarian cycle and inhibits folliculogenesis [12]. Of course, the question of the mechanisms of the toxic action of this natural polyphenol is interesting. According to foreign researchers, it is based on the ability of gossypol to induce free radical oxidation processes [12].
Summarizing the above, we can conclude that the presence of toxic effects in gossypol has limited its use in medicine for a long time. Interest in it arose as a result of the identification of new properties of its derivatives. A number of scientific studies have shown that, as a result of molecular cross-links with certain low-molecular and polymeric substances, gossypol loses its toxic properties, while its antiviral and immunomodulatory activity is retained [15-18]. The technology for producing Kagocel is based on just such a technique. Kagocel is not gossypol in its pure form. Kagocel is a high molecular weight compound synthesized based on the sodium salt of carboxymethylcellulose and the low molecular weight natural polyphenol gossypol. Carboxymethylcellulose is a polymer carrier that is a macromolecule traditionally used in the food and medical industries. At the same time, Kagocel has pronounced antiviral and immunomodulatory properties. The toxic effects of gossypol described above are not detected when using Kagocel. It is important to constantly pay close attention to ensuring that Kagocel is maximally purified from natural polyphenol impurities. Its manufacturers consider this work on creating the drug a priority. Thus, throughout the entire life cycle of the drug, research continues to confirm its safety at both the chemical and biological levels.
In order to maximize the purification of Kagocel, multiple stages of washing the resulting substance are carried out. To ensure reliable control of the content of residual gossypol impurities in a substance at a safe level, a highly sensitive spectrophotometric method has been traditionally used until now. It should be noted that the modern State Pharmacopoeia of the Russian Federation, based on world practice, recommends introducing more specific methods into the control and quality system, including HPLC. In order to introduce this technique into the control system for the production of the pharmaceutical substance "Kagocel", a modern HPLC technique with spectrophotometric detection was developed and validated for accurate and selective determination of the content of gossypol in the substance "Kagocel" [19]. This technique makes it possible to reliably detect free gossypol impurities with high reliability and accuracy at very minimal quantities, starting from 1.56·10–5 mg/ml. The indicated sensitivity of the technique corresponds to the data of foreign publications on the analysis of gossypol content using HPLC [21, 22]. When validating the method, it was proven that all gossypol introduced from outside into the substance is reliably and correctly detected in this complex, and this indicates the absence of nonspecific sorption of its free molecules on the polymer matrix. Using this technique, it was shown that the content of residual impurities of free gossypol in the drug, both immediately after manufacture and after storage during the established shelf life, is at the level of 0.0002 to 0.0030% of the mass of the substance, which is 20-100 times less than the minimum thresholds for the content of impurity components to be detected in medicinal substances established by world pharmacopoeias and the State Pharmacopoeia of the Russian Federation XIII. Such a low level of gossypol impurity guarantees the absence of adverse effects of the drug Kagocel on the human body. It should be noted that the adverse physiological effects of free gossypol are observed when it is administered in a free form per os
into the human body in doses above 0.12 mg/kg [23]. Currently, the HPLC technique is used in the production of Kagocel and provides effective control over the completeness of removal of unbound free gossypol residues. Each batch of produced substance is controlled.
Specialists from the manufacturing company, together with scientists from the Federal Research Center of Biotechnology of the Russian Academy of Sciences, also studied the possibility of “splitting off” molecules of bound gossypol as a result of prolonged exposure to components of a model environment, which are simulators of gastric and intestinal juice. These mimics may result in changes in dissolution parameters or changes in the pharmacologically active ingredient itself. The results of the study showed that with long-term (24 hours) incubation of Kagocel in the above-mentioned model media, as well as in a special medium containing microbial cellulase capable of destroying cellulose and its derivatives, there is no increase in the content of free gossypol impurities [20]. Thus, the maximum liberation of the substance from gossypol impurities, the absence of the likelihood of “splitting out” its molecule as a result of exposure to gastric and intestinal juice, as well as in an environment containing microbial cellulase, allows us to state that Kagocel does not have toxic properties characteristic of natural polyphenol. However, information guaranteeing the safety of Kagocel, in accordance with the current requirements of the Ministry of Health of the Russian Federation, can only be obtained through additional studies on biological models in vivo
and
in vitro
.
The toxicological characteristics of the drug Kagocel have been well studied both in the preclinical and clinical phases of drug development. At the stages of pre-registration preclinical studies, experiments were conducted to study acute, subchronic and chronic toxicity, as well as specific types of toxicity. Preclinical toxicological studies were carried out in leading research centers in Russia and the CIS countries. In particular, part of the preclinical toxicological studies was carried out at the Research Center for Toxicology and Hygienic Regulation of Biological Products of the Federal Medical and Biological Agency, at the Research Institute of General Pathology and Pathophysiology of the Russian Academy of Medical Sciences (Moscow), at the Research Institute of Epidemiology and Microbiology named after. N.F. Gamaleya of the Russian Academy of Medical Sciences, at the Federal State Unitary Enterprise Center for the Chemistry of Medicines VNIHFI (2006), etc. Experiments were carried out on mice, rats, rabbits and dogs. The study of acute toxicity makes it possible to determine the tolerable, toxic and lethal doses of the test drug when administered intragastrically to mice, to establish the causes of death of animals within 14 days of observation, to study its effect on the general condition and a number of functional and morphological indicators. It should be noted that the pattern of intoxication in acute toxicity experiments with free gossypol has been well studied and includes respiratory distress, weight loss, anorexia, weakness, apathy, signs of heart failure and death within a few days [12]. At the same time, data from experiments studying the acute toxicity of Kagocel showed the absence of death of animals, as well as signs of acute intoxication. When studying subchronic and chronic toxicity, all studied parameters did not differ from those in the control group of animals. The results of studies of specific types of toxicity showed that the drug does not have carcinogenic, immunotoxic, mutagenic or allergenic effects. Preclinical experiments have shown that Kagocel does not have a negative effect on all aspects of the reproductive system of animals, including does not affect the generative function of males and females, does not cause teratogenic and embryotoxic effects, and does not have a negative effect on the development of fetuses in the post- and antenatal periods of development . Thus, in preclinical experiments it was shown that Kagocel is a safe drug, while free gossypol in toxicological experiments proved to be a highly toxic compound.
During preclinical studies, the reproductive toxicity (at the stage of germ cell maturation) of Kagocel was studied in mature animals [24]. Such experiments are a mandatory stage of preclinical research. The work was carried out at the Research Center for Toxicology and Hygienic Regulation of Biological Products of the Federal Medical and Biological Agency and at the Research Institute of General Pathology and Pathophysiology of the Russian Academy of Medical Sciences (Moscow). According to methodological recommendations, these studies are carried out on rats. It is widely known that this species of animal has a reproductive system structure that is largely similar to that of humans, and the results of experiments on rats can be extrapolated to humans. As a result of research, it was established that the administration of Kagocel, both at a therapeutic dose and 25 times higher than it, daily for 70 days (the duration of the entire spermatogenesis cycle in rats) does not lead to a decrease in the fertility of male rats. Embryonic mortality rates in intact female rats mated with them did not exceed control values. The offspring of male rats treated with Kagocel showed no pathological changes or delays in physical development, and the offspring had a high survival rate. When studying the morphological and functional indicators of spermatogenesis, it was found that the mass coefficient of the testes and the caudal part of their epididymis, as well as the average number of sperm, the relative number of their immobile forms, the maximum duration of movement and the number of their pathological forms corresponded to the control values. A morphological analysis of the condition of the testes of rats treated with Kagocel did not reveal a decrease in the spermatogenesis index. There was no inhibition of proliferative activity in testicular tissue. The number of sources of proliferative spermatogenesis (normal spermatogonia) corresponded to that in the control. Thus, Kagocel did not have a negative effect on the spermatogenesis of rats, while free gossypol in large doses leads to inhibition of the maturation of male germ cells [12]. The data obtained indicate that Kagocel does not have reproductive toxicity in relation to the reproductive system of sexually mature male rats. Considering that Kagocel is indicated for the prevention and treatment of viral infections in children, it is certainly important to assess its effect on immature gonads, which are sensitive to various toxic effects [25]. In this regard, in the laboratory of the reproductive system of the Research Institute of Pharmacology and Regenerative Medicine named after. E.D. Goldberg National Medical Research Center conducted a series of experimental studies to study the long-term reproductive safety of using the drug Kagocel on immature gonads [26-28]. The studies carried out fully complied with the requirements of the current Guidelines of the Federal State Budgetary Institution Scientific Center for Emergency Medicine of the Ministry of Health of the Russian Federation for conducting preclinical studies of drugs [29]. The experiments included three series of studies. In the first series, the possible long-term toxic effect of Kagocel on the reproductive system of rats (males, females) of infantile age (10 days old) was studied. The drug was administered for 12 days. At the second stage, the state of the reproductive system of rats was studied after administration of the drug (for 48 days) in the puberty period of development (age 52-54 days). In the third series, the possible toxicity of the drug was studied after its three-time course administration (over 4 days) throughout the entire process of maturation of the gonads (infantile, prepubertal, pubertal periods of development). In all series of experiments, Kagocel was administered at a therapeutic dose and at a dose 10 times higher. The assessment of reproductive safety was carried out when the animals reached reproductive age (2.5 months), i.e., in the long term after drug exposure. The study results showed that the drug did not reduce the fertility of both male and female rats. Judging by the embryonic mortality rates, Kagocel does not cause cytogenetic changes in germ cells leading to the death of embryos, and does not increase the level of DNA breaks in germ cells in the DNA comet test. The administration of the drug did not have a toxic effect on the offspring of animals receiving the drug. The body weight of fetuses and pups, the survival index, the state of internal organs and ossification processes corresponded to control values. In histological analysis of the testes, which used morphometric indicators, the appearance of atrophied convoluted seminiferous tubules was not observed. The spermatogenic epithelium of male rats in the experimental group, as in the control group, was represented by spermatogonia, spermatocytes, spermatids, and spermatozoa. No thinning of spermatogenic tissue was detected. The lumens of the tubules remained free, and no increased exfoliation of dead cells was noted. Active processes of cell division took place in spermatocytes and spermatogonia. The number of sources of the proliferative pool of spermatogenesis corresponded to control values. The latter allows us to conclude that suppression of spermatogenesis should not be expected in the next 3 months after the end of the experiment. Sertoli cells were visible in the gaps between spermatogonia both in the experiment and in the control. Their cell membranes did not appear damaged, indicating the integrity of the blood-testis barrier. Testosterone-synthesizing cells (Leydig cells) were located between the convoluted seminiferous tubules of all examined animals. Most of them had a specific grain size. Its presence is known to be characteristic of functionally active cells. As noted earlier, the administration of gossypol has a toxic effect on Leydig cells and Sertoli cells and leads to a block of spermatogenesis, in which maturing germ cells stop proliferating. The data obtained indicate that Kagocel does not lead to pathological changes in the testes of immature animals when they reach sexual maturity. At the same time, according to the literature, the administration of free gossypol to male rats in the prepubertal and early pubertal periods of development leads to the appearance of cysts in the tail of the epididymis, which may cause infertility [12]. In this regard, when conducting experiments to study the possible reproductive toxicity of Kagocel in immature animals, a thorough external examination of the caudal part of the testicular appendages was carried out, their mass was determined and their mass coefficient was calculated. The results of the study showed that the development of cysts was not observed in male rats receiving Kagocel. Epididymal mass coefficients corresponded to control values (placebo). In these studies, the morphological state of the female gonads of rats treated with Kagocel was studied. It also turned out to be similar to that in the control. No hemodynamic changes were detected. In the tissues of the glands, follicles were identified that were at various stages of maturity: primordial, with two or more layers of granulosa cells, Graafian vesicles. In some cases, the follicles showed signs of atresia. The forming yellow bodies were also clearly visible. Thecal membranes showed no signs of disorganization. Interstitial cells maintained their integrity. The noted presence of ovulating follicles in the ovary and the fact that the fertility of rats did not decrease indicates that Kagocel does not inhibit folliculogenesis, unlike gossypol.
Thus, the administration of the drug Kagocel to immature animals does not have a negative effect on their gonads, reproductive system and offspring when they reach reproductive age. The data obtained indicate the absence of long-term effects of Kagocel on the gonads of immature animals and characterize Kagocel as a drug with a wide profile of reproductive safety. It can also be safely used in pediatric practice.
Assessing the safety of a new drug, as is known, is not limited only to experimental studies. All identified side effects of a new drug must be monitored at each stage of clinical trials in compliance with current legislation and obtaining appropriate approvals from government regulatory authorities. At the stage of phase I clinical trials of Kagocel, good tolerability of the drug in the studied doses in healthy volunteers was established, the absence of allergic reactions and toxic effects on indicators of liver and kidney function, the homeostasis system, and on immunocompetent cells. Further studies to study the therapeutic and preventive effectiveness of Kagocel for certain diseases (ARVI/influenza, herpes) and at the same time the safety of the drug were carried out in phases II and III of clinical trials. Registration randomized, blind, placebo-controlled, multicenter clinical trials of the effectiveness and safety of the drug Kagocel in adults in the treatment and prevention of influenza and other acute respiratory viral infections were conducted at the leading research institutes of Russia: Influenza Research Institute of the Russian Academy of Medical Sciences (St. Petersburg), Virology Research Institute named after. DI. Ivanovsky RAMS (Moscow) and the Military Medical Academy named after. CM. Kirov (St. Petersburg) in 2000-2002. The research results, along with effectiveness, showed the absence of side effects. Persons who took Kagocel for therapeutic and prophylactic purposes noted its good tolerability, the absence of adverse events and allergic reactions, and no complaints of discomfort in the gastrointestinal tract or other body systems were registered in the test patients. According to the results of laboratory studies, Kagocel did not have a negative effect on indicators of liver function, kidney function, or the hematopoietic system [30-33]. The data obtained during clinical trials on the safety of the drug in adults (no side effects and good tolerability of the drug), as well as the absence of adverse reactions identified during clinical trials, according to the company's pharmacovigilance service, served, along with preclinical data, as the rationale for initiating and conducting clinical studies involving children. Pediatric studies to study the therapeutic and preventive effectiveness of the drug against influenza and acute respiratory viral infections and safety were carried out sequentially in 2 stages with obtaining safety data, with a gradual decrease in age in children: aged 6 years and older (2007-2009) and age from 2 to 6 years (2010-2011). Multicenter, blind, randomized, placebo-controlled clinical trials were conducted at the clinical sites of the Research Institute of Virology named after. DI. Ivanovsky RAMS, State Educational Institution of Higher Professional Education RSMU Roszdrav, State Scientific Center “Institute of Immunology FMBA”, Federal State Institution “Moscow Research Institute of Pediatrics and Pediatric Surgery of Rosmedtechnologies”. No adverse events, toxic or allergic reactions to Kagocel were identified during its use during clinical studies. During therapy, all children showed good tolerability of the Kagocel drug and the absence of adverse reactions, which was confirmed by the absence of negative dynamics in peripheral blood parameters, general urine analysis and biochemical blood tests during follow-up [34-39]. Despite the fact that permission was received to conduct a clinical trial in children from 2 years of age and safety data were obtained in children starting from this age, the instructions for use of the drug Kagocel are approved for use in children from 3 years of age. This is due to the fact that the drug Kagocel is available in dosage form in the form of tablets, and tablets are approved for use in children only from 3 years of age. Thus, since 2008, the drug has been recommended for use in pediatric practice for the treatment of influenza and ARVI in children from 6 years of age, since 2011 - in children from 3 years of age.
In total for the period 2000 - 2011. More than 2,000 patients, both adults and children over 2 years of age, took part in clinical studies. The results of these studies demonstrated a high level of safety in the use of Kagocel, along with its high therapeutic and preventive effectiveness both against influenza caused by viruses of various types and subtypes (including pandemic), and against other acute respiratory viral infections. Data obtained from clinical studies in groups of patients with a specific nosology, which are selected strictly according to inclusion/exclusion criteria and conducted on a small sample (hundreds, thousands of patients), are very important. However, they do not provide a complete picture of the characteristics of the use and tolerability of the drug in different groups of people who may have concomitant pathology, which is often observed in clinical practice. For this purpose, phase IV studies are conducted, which are initiated after the drug receives state registration and permission for its use in widespread practice. These post-marketing studies have a number of objectives, one of which is to identify and determine previously unknown or possible drug side effects and risk factors.
In 2016, the results of a large international prospective observational study were published, in which for the first time, in outpatient practice, the treatment of ARVI and influenza with Kagocel was analyzed in 17,266 adult patients from 262 medical centers in several countries: Russia, Armenia, Moldova, Georgia. These studies showed good tolerability and effectiveness of the drug Kagocel over time, regardless of the time of administration of therapy. The drug has been shown to combine well with other drugs, including those used for the treatment of acute respiratory viral infections and influenza and the resulting complications [40-42]. Information on adverse events was obtained from 14 patients receiving Kagocel. At the same time, in the greatest number of cases, allergic reactions of mild and moderate severity were recorded. Based on the composition of the excipients included in the tablet of the drug Kagocel, contraindications to its use are increased individual sensitivity to its components, lactase deficiency, lactose intolerance and glucose-galactose malabsorption, as well as pregnancy and lactation, the age of children under 3 years.
Thus, analysis of literature data shows that the possible toxic effects of Kagocel have been sufficiently well studied in both experimental and clinical studies. In the production of Kagocel, modern methods of purifying the drug from gossypol are used. The data obtained allow us to conclude that Kagocel is a safe antiviral drug, including in reproductive terms. It is safe for use in pediatric practice.
The authors declare no conflict
of interest.
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.
Rotavirus infection: brief description
The disease has several names: in addition to the well-known “intestinal flu”, it is often called rotavirus gastroenteritis.
The causative agent of the infection is rotavirus, a spherical organism shaped like a wheel. This external similarity was the reason for the name of the disease: rota in Latin means “wheel”. The culprit of intestinal infection is distinguished by its microscopic size and extraordinary vitality. This is explained by its structure: the body is protected by a three-layer shell, which reliably shelters the pathogen from external influences and enzymes of the digestive tract.
Thanks to its special structure, the pathogen remains viable for a long time in an aggressive environment: it tolerates cold well, does not die in water, and persists for a long time on various surfaces, feces and food.
Rotavirus is resistant to most chlorine-containing disinfectants. Formaldehyde and ether are also powerless against it. It can only be eliminated by high temperatures (for example, boiling), alkaline agents and acids.
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.
Signs of rotavirus infection
The latent period after infection of the body lasts from 1 to 5 days, then the disease manifests itself very violently and in an acute form. Its main features are:
- Attacks of vomiting. At first, the vomit is copious, with food particles, then becomes watery.
- Severe abdominal pain: can be constant or sharp, cramping. Localization - in the epigastric or navel area.
- Increased temperature (37.5-38 °C).
- Frequent diarrhea: happens 5-15 times a day. The stool is yellow or greenish, foaming, with a pungent odor.
Headache, weakness, dizziness, fainting or convulsions are also possible.
The prognosis of the disease is usually favorable; death occurs in isolated cases - mainly in children under 12 months of age. Occurs due to severe dehydration, disruption of the cardiovascular system and kidneys.
The danger of rotavirus lies in possible complications: in the absence of proper treatment, another viral or bacterial infection may occur.
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.
