Tiloron-sz 125 mg 6 pcs. film-coated tablets
Composition and release form Tiloron-sz 125 mg 6 pcs. film-coated tablets
One film-coated tablet contains:
- active ingredient: tilorone dihydrochloride - 125 mg;
- excipients (core): microcrystalline cellulose - 105.0 mg; potato starch - 46.0 mg; hypromellose (hydroxypropyl methylcellulose) -4.0 mg, hyprolose (hydroxypropylcellulose) -17.0 mg; magnesium stearate - 3.0 mg; excipients (shell): Opa-dry II 85F220184 - 9.0 mg (macrogol (polyethylene glycol) 3350 - 2.7890 mg; talc - 1.1806 mg; titanium dioxide E 171 - 1.1874 mg; dye-based aluminum varnish sunset yellow E 110 - 1.3315 mg; iron oxide yellow E 172 - 1.1800 mg, indigo carmine dye E 132 - 1.3315 mg).
Film-coated tablets, 125 mg. 6 or 10 tablets in a blister pack made of PVC film and aluminum foil. 20 tablets in a polymer jar made of low-density polyethylene with a lid made of high-density polyethylene or in a polymer bottle made of low-density polyethylene with a lid made of high-density polyethylene. Each jar, bottle, 1 blister pack of 6 tablets or 1 blister pack of 10 tablets, along with instructions for use, is placed in a cardboard box.
Description of the dosage form
Film-coated tablets.
Characteristic
The tablets are round, biconvex, orange film-coated. In a cross-section, the core of the tablet is orange with minor white inclusions.
Directions for use and doses
Tilorone is taken orally after meals. For the treatment of influenza and other acute respiratory viral infections - 125 mg per day for the first 2 days of treatment, then 125 mg after 48 hours. Per course - 750 mg (6 tablets). For the prevention of influenza and other acute respiratory viral infections - 125 mg once a week for 6 weeks. Per course - 750 mg (6 tablets). For the treatment of herpes infection - the first two days, 125 mg, then after 48 hours, 125 mg. The course dose is 1.25 - 2.5 g (10-20 tablets). When treating influenza and other acute respiratory viral infections, if symptoms of the disease persist for more than 4 days, you should consult a doctor.
Pharmacokinetics
After oral administration, it is quickly absorbed from the gastrointestinal tract. Bioavailability - 60%. About 80% of the drug binds to plasma proteins. The drug is excreted almost unchanged through the intestines (70%) and through the kidneys (9%). The half-life (T1/2) is 48 hours. The drug does not undergo biotransformation and does not accumulate in the body.
Indications for use Tiloron-sz 125 mg 6 pcs. film-coated tablets
- treatment of influenza and other acute respiratory viral infections;
- treatment of herpes infection;
- prevention of influenza and other acute respiratory viral infections in adults.
Contraindications
- hypersensitivity to tilorone or any other component of the drug;
- pregnancy and breastfeeding period;
- children's age (up to 18 years).
Application of Tiloron-sz 125 mg 6 pcs. film-coated tablets during pregnancy and breastfeeding
The drug is contraindicated during pregnancy. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.
Overdose
Cases of drug overdose are unknown.
Side effects Tiloron-sz 125 mg 6 pcs. film-coated tablets
Allergic reactions, dyspepsia, short-term chills are possible. If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.
Drug interactions
Compatible with antibiotics and drugs for traditional treatment of viral and bacterial diseases. No clinically significant interaction of tilorone with antibiotics and traditional treatments for viral and bacterial diseases has been identified.
Treatment and prevention of chronic infections is a task that more than one generation of scientists has been working on. Any decrease in the effectiveness of the immune response (adverse effects of environmental factors, intoxication, long-term use of antibacterial drugs, genetic factors, age, etc.) can lead to relapse or development of a chronic process. The search and implementation of drugs that combine antiviral and antibacterial activity with immunomodulatory properties in this regard are of particular relevance. In our country, this niche has been firmly occupied by a group of interferon inducers (IFNs). The history of studying IFN inducers goes back more than 40 years. The idea of “switching on” the synthesis of the body’s own (endogenous) IFN, called “endogenous interferonization,” arose after the presence of IFN genes was proven in almost all cells of the body (Steinebring, Youngner, 1964). For example, in response to viruses (which happens all the time), a healthy body responds with the formation of IFN, thereby preventing the subsequent development of the infectious process. The use of IFN inducers does not have the disadvantages of recombinant IFNs (primarily antigenicity) and in some cases is their full replacement. The advantages of IFN inducers include the physiological synthesis of the body’s own (endogenous) IFN, prolonged production of IFN even with a single administration of the inducer, and antiviral effect [1].
There are two main classes of IFN inducers - natural and synthetic, which in turn are divided into high molecular weight (allokin-α, inosine pranobex, immunomax, poludan, etc.) and low molecular weight ( Lavomax
, cycloferon). As a result of many years of targeted screening among compounds of different nature (fluorenone derivatives, gossypol analogues, synthetic polynucleotides, natural double-stranded RNA, etc.), promising IFN inducers were identified that have a fairly high chemotherapeutic index, which can be used for the treatment and prevention of a wide range of viral infections and a number of infectious diseases accompanied by IFN-deficient conditions.
Each of the IFN inducers has a spectrum of therapeutic activity and at the same time has its own “points of application” in the immune system. For example, cycloferon causes rapid production of α-IFN by peripheral blood leukocytes (leukocyte mechanism), while Lavomax
slowly induces the production of γ-IFN by T lymphocytes during the activation process - upon interaction with an antigen-presenting macrophage (immune mechanism) [2].
Inducers also differ markedly in their ability to “switch on” the synthesis of IFN in different organs (brain, lungs, liver, spleen, etc.). Knowledge of the features of the mechanism of action of individual IFN inducers is important for a practicing physician, since this undoubtedly affects the tactics of their use in different types of organ pathology. In this regard, we have made an attempt to summarize scientific research data and clinical experience on the use of the oral IFN inducer tilorone ( Lavomax
) both in Russia and abroad.
Lavomax
(tilorone) is an aromatic hydrocarbon of synthetic origin (fluorenone), which is distinguished by its comparative simplicity of structure, has antiviral properties and the ability to induce IFN when administered orally. Being a low-molecular compound (molecular weight 483.47), tilorone is characterized by the absence of antigenic activity, which is important when used in complex therapy of patients with endocrine pathology.
Tiloron is registered in Russia ( Lavomax
, Amiksin) and in Ukraine (Tilaxin) as an antiviral and immunomodulatory drug. Tiloron is also produced in Italy (Erregierre SpA) and China (Tiloron), where it is registered as an antiviral drug for the treatment of tumors. In dosage forms in Russia and abroad, the tilorone compound is used in the form of dihydrochloride. By order of the Government of the Russian Federation No. 2135 of December 30, 2009, tiloron was included in the list of vital medicines, taking into account its study and safety.
The first mention of 2,7-bis-[2-(diethylamino)ethoxy]fluorenone-9 is found in US patent application No. 788,038 dated December 30, 1968 (US patent No. 3,592,819), which describes the synthesis process (among other compounds , which later received the common name “tilorone analogs” - Tilorone Analogs) and its antiviral properties. The first articles devoted to tilorone as an oral antiviral agent were published in 1970 by G. Mayer and R. Krueger in the journal Science, one of the most authoritative scientific publications in the USA [3, 4]. In 1973, an article by G. Mayer and R. Krueger was published in the journal Antibiotics by Z.V. Ermolyeva et al. [5], dedicated to the interferonogenic properties of tilorone. This article aroused the interest of Soviet scientists in tiloron. In 1975, at the Physicochemical Institute of the Ukrainian SSR Academy of Sciences (Odessa), L.A. Litvinova et al. [6] synthesized tilorone for the first time in the USSR. D. Stringfellow, who devoted many years to the study of tilorone, defined it as a non-polynucleotide IFN inducer with a wide range of pharmacological activities - antitumor, antiviral, immunomodulatory and the ability to induce endogenous IFN [7, 8]. Such an unusual combination of properties of tilorone at that time led to many years of scientific and clinical research in many countries around the world [9–11].
As a result of numerous studies, the immunological properties of tilorone in vitro and in the human body were identified and described in detail. The effect of the drug is aimed at correcting disorders of both innate (nonspecific) and adaptive immunity. Being a polyclonal stimulant, tilorone includes a fast-acting link of natural immunity - the IFN system (synthesis of α-, β- and γ-IFN in enterocytes, hepatocytes, T-lymphocytes, neutrophils, granulocytes and other cells) and the primary immune response, activates cellular mechanisms, which together interrupt the reproduction of viruses and other intracellular agents (chlamydia) in infected cells, cause their death and contribute to the elimination of pathogens.
The first target of contact and exposure to tilorone is the gastrointestinal tract (GIT). The works of G. Grass [12], R. Owen [13] show that more than 25% of the surface of the small intestine is occupied by areas of lymphoid tissue called Peyer's patches, which are an excellent place for the direct absorption of any antigens. Peyer's patches are gut associated lymphoid tissue (GALT) and were described by A. Besredska (1927), T. Tomasi and J. Bienenstock (1968). They are able to mount a local immune response and produce specific antibodies to orally administered antigens. The epithelium of Peyer's patches contains microfolded cells (M cells). M cells recognize immunoactive substances and bring them into contact with the first cellular elements of the immune system, namely APCs, T cells and B cells. As a result, secretory antibodies are produced, in particular sIgA, some of which return to the epithelium and are released into the intestinal lumen. Secretory sIgA is also synthesized by the membranes of the mucous membrane of the gastrointestinal tract, urogenital and respiratory tracts, as well as the salivary and lacrimal glands. That is why, as a result of immunization in the gastrointestinal mucosa, antibodies to a specific antigen (antigen-specific antibodies) can appear in the mucosal tissues of the entire body. Tiloron is an oral immunostimulating drug that activates the mechanism of the adaptive immune response through the lymphoid tissue of the mucous membranes of not only the gastrointestinal tract, but also the pulmonary and urogenital tracts (MALT, GALT and UALT) and maintains the activity of innate immune mechanisms at a high level.
Tilorone is the first oral effective small-molecule IFN inducer [4, 7]. In humans, the peak of IFN production in the blood is determined 20-24 hours after taking the drug. In terms of the amount of endogenous IFN induced in the blood, a single dose of tilorone at a dose of 125 mg is comparable to the intramuscular administration of exogenous human recombinant α2-IFN (reaferon) at a dose of 3 × 106 IU, the content of which, as a result of proteolysis, progressively decreases after 6-8 hours. Maximum IFN production in the blood reaches an average of 64-128 U/ml after a 4-fold dose of tilorone, which persists until the 8th week inclusive [14].
Lavomax
penetrates the blood-brain barrier and induces the formation of IFN in neuroglial cells and neurons of the brain [15]. Data have been published on the effect of low-molecular-weight tilorone and its analogues on the activation of a specific neuropeptide (Hypoxia-inducing Factor-1), which ensures the prevention of stroke and vascular damage in the spinal cord [16, 17].
It has been shown that tilorone leads to a noticeable and significant increase in IFN titers in individuals with low background values [18]. The presence of conflicting results on the induction of endogenous IFN in experimental animals obtained in different countries at different times is partly explained by the difference in dosages used and routes of administration [19–21]. Thus, it was demonstrated that when administered orally to mice in doses of 50 and 125 mg/kg, tilorone provided 80-90% protection of animals from 10-100 LD50 of the Rift Valley fever virus with 100% mortality of animals in the control. The titers of induced IFN reached 640 U/ml. However, with intramuscular administration of tilorone, the survival rate of animals was only 20%, and IFN titers differed little from those in the control [22]. In another study, the dose of tilorone at which an increase in IFN production was observed in rats was at least 150 mg/kg body weight per day [23].
Tilorone, like other IFN inducers, is characterized by the phenomenon of hyporeactivity - a decrease in the level of IFN synthesis in response to repeated administration of the inducer after a short interval [24]. Recovery from hyporeactivity occurs 6-7 days after the last administration of tilorone. When using the drug 2 times a week, the synthesis of IFN increases - the sensitivity of target cells to their own interferons increases. The antiviral state in the hyporeactivity phase is preserved [23]. Hyporeactivity is overcome by the administration of prostaglandins, in particular E2 [25]. It is suggested that the effectiveness of tilorone as an interferonogen may be affected and reduced by concomitant use of drugs that reduce prostaglandin production (for example, non-steroidal anti-inflammatory drugs).
The immunomodulatory effect of tilorone lies in its effect on adaptive immunity: induction of CD8+ both T-cytotoxic cells (lysis of infected cells) and TH1, which have CD4+ receptors on their surface (activation of macrophages that eliminate antigens using phagocytosis and natural cytotoxic lymphocytes - NK -cells) [26, 27]. The effect of tilorone on the production of cytokines and the activation of TH1 antiviral immunity, which ensures the antiproliferative effect of the drug, has found practical application in the complex treatment of hyperplastic processes of the larynx and vocal cords [28]. In chronic hyperplastic laryngitis and contact granulomas, DNA of the Epstein-Barr virus or other herpesviruses (HSV, CMV) is detected in scrapings in 70–77% of cases. In 2001, the antiproliferative effect of the drug was shown in the treatment of laryngeal papillomatosis [29]. This was the reason for further research into the effectiveness of Lavomax
in the treatment of human papillomavirus infection of other localizations [30–32].
According to E.A. Snisarenko et al. [31], the use of Lavomax
in the complex therapy of human papillomavirus infection of the cervix led to clinical and laboratory recovery in 91.4% of women.
E.I. Kasikhina [32] demonstrated the successful treatment with Lavomax
in the absence of effect against the background of traditional therapy.
Lavomax
has a stimulating effect on nonspecific immune reactions.
The activating effect of tilorone on macrophages is characterized not only by an increase in the absorption capacity of phagocytes, but also by the production of reactive oxygen species, nitriles, and perchloric acid by these cells, which have a bactericidal effect [33, 34]. Clinicians use this property of the drug in the complex correction of dysbiotic conditions of the urogenital tract and for local vaginal infections. Changes in the parameters of cellular immunity and phagocytosis predispose to the recurrent course of genital candidiasis [35, 36]. It is known that the ability of the vaginal environment to selectively support the growth of resident microorganisms and inhibit the growth of pathogens directly depends on the activity of neutrophils [37]. Frequent changes in antifungal agents and the use of drugs without taking into account species sensitivity can contribute to the chronicity and recurrence of candidal infection precisely due to the effect on the function of neutrophils. A decrease in the functional activity of T-lymphocytes, natural killer cells, suppression of the phagocytic and antimicrobial properties of monocytes and granulocytes occurs with hormonal disorders (hyperglycemia, thyroid pathology, hormone-dependent gynecological diseases) [36, 38]. Spanish scientists have shown a correlation between decreased NK cell function and resistance to therapy in acute systemic candidiasis in experimental animals. When using tilorone, the phagocytic activity of splenic macrophages (through activation of NK cells), the expression of class II histocompatibility complex (MHC) receptors and their production of pro-inflammatory cytokines - interleukin 6 (IL-6), IL-12 and tumor necrosis factor α (TNF- α)[39]. TNF-α is a major mediator of the inflammatory response and septic shock, the production of which by monocytes in response to the presence of infecting microorganisms and other cytokines varies significantly among individuals and is under genetic control. At the same time, TNF-α is a modulator in the vaginal microenvironment, linking changes in the vaginal microflora and the inflammatory response. These data served as the basis for determining the clinical effect of Lavomax
in chronic recurrent vulvovaginal candidiasis and bacterial vaginosis [40, 46].
Inclusion of the drug Lavomax
in the complex therapy of chronic recurrent vulvovaginal candidiasis in a study by E.I.
Kasikhina (2010) was justified by the multifocal nature of the process, a decrease in the functional activity of neutrophils in all examined patients, and the identification of latent forms of herpes viral diseases in 10.3% of women. The effectiveness of complex therapy, including the immunomodulator Lavomax
and the intravaginal antimycotic Livarol, was 97.4% at a 6-month follow-up [40]. In another study, Candida was undetectable at 3–4 months of follow-up [41].
Experimentally and based on clinical studies, it has been shown that tilorone ( Lavomax
) indirectly suppressing the growth of opportunistic microorganisms by enhancing the production of endogenous IFNs, affects the state of the microbiocenosis of the genital and intestinal biotopes, and helps restore their colonization resistance [34, 42-44].
In patients with nonspecific colpitis and cervicitis who received Lavomax
, inflammatory phenomena stopped more quickly, titers of opportunistic microorganisms decreased, lactobacilli predominated in cultural studies, and there was an improvement in general condition [45].
O.I. Letyaeva, O.A. Giesinger conducted an open randomized clinical study of the effect of the drug Lavomax
on anti-infective defense factors and microbiocenosis of the lower reproductive tract of women with chlamydial infection complicated by bacterial vaginosis.
The effectiveness of complex therapy with the inclusion of Lavomax
has been proven by clinical recovery, high frequency of eradication of C. trachomatis, normalization of indicators of mucosal immunity (TNF-α, IL-1α, IL-8, IFN-γ, IgA) and restoration of normal resident vaginal flora [46].
Immune reactions are the most important link in the pathogenesis of inflammatory diseases of the pelvic organs, largely determining the individual characteristics of the course and outcome of the disease. In this case, a restructuring of immune homeostasis occurs, affecting almost all stages of differentiation and proliferation of immunocompetent cells, resulting in the appearance of numerous functionally inferior populations lacking phagocytic activity, regardless of the type of pathogen [47]. Lavomax
, in addition to normalizing the functioning of the macrophage unit, has anti-inflammatory activity, enhancing the effect of antibacterial agents.
According to domestic scientists, the use of the drug Lavomax
in complex therapy led to a faster and more pronounced clinical effect than monotherapy with antibiotics.
Due to these properties, Lavomax
is widely used in venereological and gynecological practice as part of complex therapy for patients with complicated sexually transmitted infections, treatment of inflammatory diseases of the uterine appendages, and endometriosis [41, 48-50].
In the complex treatment of urogenital diseases associated with chlamydial, mycoplasma, fungal and bacterial infections, as well as their combinations Lavomax
used according to the following scheme: 0.125 g/day during the first two days, then after 48 hours (per course 1.25–2.5 g).
Clinical and experimental data on the use of Lavomax
for various urogenital pathologies have become a theoretical prerequisite for improving the technique of IFN therapy for urogenital chlamydia [51, 52].
The results of a comparative randomized clinical study of the effectiveness and safety of the drug Lavomax
, conducted by the Federal State Institution Research Institute of Urology of the Russian Health Service, indicate that its use contributes to a statistically significant, more effective elimination of
Chlamydia trachomatis
[51].
I.G. Leontyev [53] successfully used Lavomax
for outpatient treatment of urogenital chlamydia in men.
The etiological cure of patients in the main group who received Lavomax
was 97.05%, in the control group - 86.6% (p <0.01).
The drug can be used in the complex treatment of chronic bacterial prostatitis [54]. A randomized study conducted by a team of authors at the Ural Research Institute of Dermatovenereology and Immunopathology demonstrated the significant effectiveness of Lavomax
in the complex treatment of non-gonococcal urethritis [55].
The antiviral activity of fluorenones is also characterized by a universal breadth of action [56]. A distinctive feature of tilorone is the ability to cause long-term circulation in the blood of therapeutic doses of IFN, which prevent infection of uninfected cells and create a barrier antiviral state, suppress the synthesis of virus-specific proteins and intracellular proliferation of viruses. A. Arena et al. [57] studied the antiviral and immunomodulatory activities of different tilorone compounds. The experiment showed an increase in the activity of peripheral blood mononuclear cells and increased cytotoxicity against HSV type 2 due to the production of IFN-α and TNF-α. It should be noted that studies conducted in the 70-80s of the 20th century demonstrated the ability of tilorone to prevent the death of experimental animals when infected with HSV type 2, vesicular stomatitis viruses, encephalomyocarditis, and influenza A2 [58-60]. It has been established that Lavomax
(tilorone) has the ability to bind firmly to DNA and RNA ribonucleoproteins, suppressing the processes of synthesis of viral nucleic acids, inhibiting the processes of viral replication, and thereby exhibits direct antiviral activity against a wide range of viruses (influenza, hepatitis, a group of herpes viruses, papillomaviruses, adenoviruses and etc.).
The pharmacological antiviral effect of tilorone is due to the inhibition of reverse transcriptase of RNA-containing viruses, as a result of which their reproduction is suppressed. The combined use of antiviral chemotherapy drugs and tilorone provides an additive or synergistic effect, makes it possible to influence the pathogenetic basis of recurrent herpes infection (HSV-1, HSV-2, cytomegalovirus infection) and ensure a reduction in the dose of antiviral chemotherapy, reduces the likelihood of the emergence of resistant strains of viruses [11]. The results of numerous studies and comparative studies indicate the high effectiveness of the drug in the treatment of herpetic infections of different localizations [61-64]. An anti-relapse 2-month course of Lavomax
was more effective than a similar course of acyclovir in patients with frequently recurrent genital herpes in combination with infertility or recurrent miscarriage [65].
The antitumor and anti-inflammatory properties of tilorone are of scientific interest. R. Adamson (1971) showed that tilorone (30-60 mg/kg, ip daily, optimal dose - 30 mg/kg) increased the average life expectancy of animals inoculated with ascitic Walker 256 carcinosarcoma by 8 times. . Rifampicin (10-100 mg/kg, optimal dose - 100 mg/kg) and polyI-polyC (IFN inducer; 5-20 mg/kg, optimal dose - 10 mg/kg) provided only 2.25- and 2-fold an increase in the average life expectancy of animals accordingly [66].
Spanish and British researchers have repeatedly shown the antitumor activity of oral tilorone and inhibition of metastasis in experimentally induced fibrosarcoma and B-16 melanoma in mice. Experiments noted an increase in the activity of NK cells in the spleen [67–69]. Nevertheless, there is selectivity in the antitumor effect of tilorone. A randomized trial using tilorone was registered in 1981, studying a number of drugs for the treatment of metastatic breast cancer. In this study, tilorone had the lowest survival rates compared with other drugs used [70].
It is assumed that tilorone has anti-inflammatory activity that is not associated with stimulation of IFN production [71, 72]. The anti-inflammatory activity of tilorone may be mediated by the cholinergic anti-inflammatory cascade (COA), since tilorone has been shown to be a selective partial agonist of α7-nicotinic acetylcholine receptors [72–74]. As an inducer of COD, tilorone is able to suppress the synthesis of proinflammatory cytokines, which play a decisive role in the development of pneumonia (due to necrosis, massive damage to the alveoli and hemorrhage) in individuals infected with swine flu (H1N1) [75, 76].
At the same time, tilorone suppresses tuberculin-type cellular immunity reactions. This ability is associated with its effectiveness in experimental allergic encephalomyelitis and rheumatoid arthritis [77]. Z.Sh. Garayeva [78] successfully used Lavomax
in patients with severe forms of psoriasis, including psoriatic arthritis. It is believed that a decrease in the intensity of the immune response, which occurs as a delayed-type hypersensitivity reaction, is due to the activation of suppressor T lymphocytes. Tilorone does not affect the generation of effector cells of a delayed-type hypersensitivity reaction, but changes their properties, in particular their ability to circulate.
Data on the pharmacokinetics and drug interactions of tilorone with other drugs began to appear in the literature in 1977 [79]. After oral administration, the drug is quickly absorbed into the gastrointestinal tract, its bioavailability is 60%, and plasma protein binding is about 80%. Tiloron does not undergo biotransformation and does not accumulate in the body; it is excreted unchanged in feces and urine. These properties were confirmed by testing the safety of tilorone and IFN induction on volunteers in 1971 [80]. In a small study of 14 patients prescribed tilorone, the drug caused retinopathy and keratopathy in 2 people (doses received were 152 and 189 g, corresponding to 1216 and 1512 tablets of 125 mg each, with a recommended dose of 80-100 tablets per year). visual acuity did not decrease, and these effects were gradually reversible after cessation of treatment [81, 82]. The half-life is 48 hours. Due to the expansion of clinical indications for the use of tilorone, especially in oncology, it is necessary to control the concentration in biological fluids of the body. To quantify the drug in blood and urine, a liquid chromatography tandem mass spectrometry method was developed. Data from control studies conducted in healthy volunteers were published in 2008 and 2010 [83, 84].
IFN inducers, including tilorone, can reduce the activity of the enzyme system - cytochrome P-450. It is assumed that this effect is due to the inducible IFN itself, since a similar decrease in the activity of a number of CYP isoforms has been shown upon direct administration of IFN [85, 86]. Thus, when prescribing tilorone, the possibility of reducing the rate of cytochrome P-450 mediated metabolism of other drugs should be taken into account and, possibly, their dosage and/or administration regimens should be adjusted accordingly.
It has been established that tilorone has both cationic and lipophilic groups in its structure. Therefore, the enhanced effect with the simultaneous administration of drugs with the same chemical structure, for example, amiodarone, azithromycin, gentamicin, bromhexine, erythromycin, is understandable [87].
The combined use of tilorone and metronidazole made it possible to significantly reduce the frequency and severity of side effects associated with the hepatotoxicity of metronidazole. The same mechanism is likely responsible for the antimutagenic and anticarcinogenic activities of tilorone [88–90].
Many drugs are metabolized and inactivated in the body by acetylation. The rate of acetylation is determined largely genetically and can also vary under the influence of other drugs. Since tilorone undergoes processing in the endoplasmic reticulum, where acetyltransferase is present, its influence on acetylation cannot be excluded.
A possible connection between the use of tilorone and the process of acetylation of the model substance procainamide in rats was studied experimentally (in rats) [91]. Preliminary use of tilorone led to a 1/3 increase in the rate of acetylation, which may require additional adjustment of doses of drugs that are potentially susceptible to acetylation, such as sulfonamide drugs, anti-tuberculosis drugs (ftisopyram, isoniazid) and others.
R. Drobitch et al. [92] 48 hours after administration of tilorone to rats at a dose of 50 mg/kg, the processes of procainamide acetylation were assessed (taking into account the half-life of the drug). The acetylating activity of the blood and kidneys was not impaired. N-acetyltransferase activity was preserved. The content of hepatic acetyl coenzyme A was completely restored.
Conclusion
The data presented in the review indicate that extensive experience has been gained in the clinical use of Lavomax
, its main biological and pharmacological effects have been studied, indications and regimens of use have been developed.
Experience with the use of Lavomax
confirms its effectiveness in urogenital chlamydia, herpesvirus infections, HPV, chronic prostatitis, and dysbiotic disorders of the urogenital tract. At the same time, research continues to study the antifibrosing properties of tilorone. This promising direction is focused on the use of the drug in oncology (for fibrosarcoma and other tumors), pulmonology (for the treatment of fibrosis in pulmonary silicosis).
