Ergoferon^® (Tablets, Solution) Instructions for Use

ATC Code

L03AX (Other immunostimulants)

Clinical-Pharmacological Group

Antiviral and immunostimulating drug

Pharmacotherapeutic Group

Antiviral and immunostimulating agent

Pharmacological Action

Mechanism of action and pharmacodynamic effects

The spectrum of pharmacological activity of the drug Ergoferon^® includes antiviral, immunomodulatory, antihistaminic, and anti-inflammatory effects.

The components included in the drug have a single mechanism of action in the form of increasing the functional activity of the CD4 receptor, receptors to interferon gamma (IFN-γ) and histamine, respectively, which is accompanied by a pronounced immunotropic effect.

It has been experimentally proven that antibodies to IFN-γ: increase the expression of IFNγ, IFNα/β, as well as associated interleukins (IL-2, IL-4, IL-10 and others), improve ligand-receptor interaction of IFN, restore cytokine status; normalize the concentration and functional activity of natural antibodies to IFNγ, which are an important factor in the body’s natural antiviral tolerance; stimulate interferon-dependent biological processes: induction of expression of major histocompatibility complex antigens of types I and II and F_c receptors, activation of monocytes, stimulation of the functional activity of NK cells, regulation of immunoglobulin synthesis, activating a mixed Th1 and Th2 immune response.

Antibodies to CD4, probably being allosteric modulators of this receptor, regulate the functional activity of the CD4 receptor, which leads to an increase in the functional activity of CD4+ lymphocytes, normalization of the immunoregulatory index CD4+/CD8+, as well as the subpopulation composition of immunocompetent cells (CD3+, CD4+, CD8+, CD16+, CD20+).

Antibodies to histamine modify histamine-dependent activation of peripheral and central H₁ receptors and, thus, reduce the tone of bronchial smooth muscles, reduce capillary permeability, which leads to a reduction in the duration and severity of rhinorrhea, swelling of the nasal mucosa, coughing and sneezing, as well as a reduction in the severity of allergic reactions accompanying the infectious process by suppressing the release of histamine from mast cells and basophils, the production of leukotrienes, the synthesis of adhesion molecules, and reducing eosinophil chemotaxis and platelet aggregation in reactions to contact with an allergen.

The combined use of the components of the combination drug is accompanied by an enhancement of the antiviral activity of its components.

During experimental and clinical studies, therapeutic efficacy against influenza viruses, parainfluenza, rhinovirus, metapneumovirus, seasonal strains of coronaviruses, bocavirus, respiratory syncytial virus, respiratory and intestinal strains of adenovirus, rotaviruses, noroviruses, astroviruses, as well as non-specific preventive efficacy against SARS-CoV-2 has been established. In a clinical study, the risk of COVID-19 disease was reduced by 3 times during the vaccination period between the administration of the I and II components of the Gam-COVID-Vac vaccine against the background of prophylactic use of the drug Ergoferon^®.

Clinical efficacy and safety

The efficacy and safety of the drug Ergoferon^® has been demonstrated in a series of multicenter clinical studies with placebo and active control.

The results of a multicenter open comparative randomized clinical study of the efficacy and safety of the use of the drug Ergoferon^® in the treatment of influenza showed that the drug Ergoferon^® is an effective and safe drug.

The primary efficacy criterion in the influenza treatment study was the proportion of patients with a decrease in axillary temperature to 37°C (98.6°F) and below (without subsequent increase) during the observation period. The percentage of patients with normal morning body temperature increased in the Ergoferon^® group from 19% on the second day (versus 10% in the Oseltamivir group) to 100% by the end of the treatment course (versus 92% in the Oseltamivir group). Evening thermometry showed that by the end of day 4, more than two-thirds of patients (68%) had a body temperature of ≤37°C (98.6°F), and by the end of day 5, normalization of temperature was noted in the vast majority (85%) of patients in the Ergoferon^® group. The indicators in the Oseltamivir group were approximately the same (from 69% to 86%, respectively). Frequency analysis showed that the drug Ergoferon^® had a positive therapeutic effect on the febrile reaction, which is known to be a marker of the activity of the infectious process in influenza, and this effect was similar to the action of Oseltamivir. In addition, the percentage of patients who had no clinical manifestations of influenza on day 7 of participation in the study, including fever, intoxication and respiratory symptoms, which were assessed by the doctor on a 4-point scale (from 0 to 3), was additionally assessed. Headache, as well as other types of pain (muscle, joint, in the eyeballs), was absent in 99% of participants in the Ergoferon^® group and 100% in the Oseltamivir group; asthenic manifestations (weakness, sweating, malaise, drowsiness) – in 82%, 87%, 90%, 96% and 74%, 86%, 91% and 97% of patients, respectively. All intoxication symptoms were completely relieved by day 7 in 60% and 64% of participants, respectively. Catarrhal symptoms, persisting for more than a week in a small percentage of patients, were completely absent on day 7 in 83% of patients in the Ergoferon^® group and in 77% of patients in the Oseltamivir group. The proportion of patients without any flu symptoms was 45% in the Ergoferon^® group and 50% in the Oseltamivir group. Thus, the results of the analysis indicated that the five-day course of therapy with the drug Ergoferon^® was reliably comparable to therapy with Oseltamivir.

Significant and positive clinical dynamics against the background of therapy with the drug Ergoferon^® and Oseltamivir had a similar effect on the need for patients to use symptomatic therapy (antipyretics). If on the first day of participation in the study many patients used permitted antipyretic drugs (on average with a frequency of 0.65±0.48 per patient in the Ergoferon^® group and 0.69±0.46 in the Oseltamivir group), then in the next 2 days their use sharply decreased (to 0.19±0.40 and 0.15±0.36 on the third day, respectively). On the following days 4 and 5, only individual participants in both groups took antipyretics.

The average total score of the quality of life questionnaire (European Quality of Life Questionnaire) in patients of the Ergoferon^® group over 7 days changed almost 2 times and amounted to 5.4±0.8 versus the initial 9.4±1.9 points, reflecting positive changes in the quality of life of the study participants. In the comparison group, the corresponding figures were 5.5±0.9 and 9.2±2.3 points, respectively.

The results of a multicenter double-blind placebo-controlled randomized clinical study of the efficacy and safety of the use of the drug Ergoferon^® showed that Ergoferon^® is an effective and safe drug in the treatment of acute respiratory viral infections of various etiologies.

Treatment with the drug Ergoferon^® led to normalization of body temperature significantly faster and in a larger percentage of patients compared with placebo therapy. Comparison of the proportions of patients in the two groups according to morning and evening thermometry indicators on each of the five days of treatment revealed a significant difference between the Ergoferon^® and placebo groups over the entire time period, including five pairs of measurements (p<0.05). The effectiveness of the drug Ergoferon^® manifested itself one day after the start of therapy, which was confirmed by the predominance of patients with normal body temperature (≤37°C (98.6°F)) in the active drug group, starting from the second day. On the third day of treatment, the proportion of patients without fever during the day in the Ergoferon^® group exceeded half, and until the end of observation remained greater than in the placebo group. The duration of the febrile period in most patients (74%) was limited to three days; about a third of the study participants who received the drug Ergoferon^® had elevated body temperature only in the first two days.

The effectiveness of treatment with the drug Ergoferon^® was also confirmed by a lower frequency of antipyretic drug use. The proportion of patients taking antipyretics in the Ergoferon^® group was significantly lower than in the placebo group throughout the entire course of treatment. Starting from the fourth day of therapy, patients receiving the drug Ergoferon^® did not need to take antipyretic drugs.

The drug Ergoferon^® had a positive effect on other general intoxication and respiratory manifestations of the disease, including asthenic (weakness, malaise) and catarrhal (nasal obstruction and nasal discharge) symptoms, which on the third day of treatment were less pronounced than in patients in the placebo group. Early initiation of therapy with the drug Ergoferon^® had a more pronounced clinical efficacy. A significant treatment effect was manifested in the dynamics of the temperature reaction: on the third day, fever was absent in most patients (mean axillary temperature 36.8±0.3°C (98.2°F)). The average severity of headache on the third day decreased by 80%; by day 7, no patient in the Ergoferon^® subgroup reported cephalgia. A similar dynamic was observed for asthenic symptoms, drowsiness, sweating, pain in the eyeballs, rhinorrhea and sore throat. On the third day, the proportion of patients without clinical manifestations of ARVI in the Ergoferon^® group was 50% (versus 8% in the placebo group), and the proportion of patients without complaints of headache and drowsiness (100%) significantly exceeded the corresponding indicators in the placebo group. By the end of the five-day course of treatment, almost all patients receiving the drug Ergoferon^® were healthy (92% versus 75% in the placebo group).

The results of an international multicenter double-blind placebo-controlled randomized clinical study of the efficacy and safety of the use of the drug Ergoferon^® showed that the drug Ergoferon^® is an effective and safe drug in the treatment of acute respiratory viral infections in children.

The time to resolution of all ARVI symptoms against the background of treatment with the drug Ergoferon^® was 4.5±1.7 days (versus 5.2±2.2 days in the placebo group; p=0.026). In 25% of children in the Ergoferon^® group, the disease lasted less than 3 days, in 25% of children in the placebo group the disease lasted more than 7 days (due to a protracted or complicated course of ARVI). The average duration of fever in the Ergoferon^® group was 2.8±1.5 days (versus 3.4±2.0 days in the placebo group; p=0.031). In 25% of children in the Ergoferon^® group, body temperature normalized in less than 2 days, in 25% of children in the placebo group, fever continued for more than 5 days (due to a complicated course of ARVI). The time to resolution of general ARVI symptoms in children of the Ergoferon^® group was 4.0±1.8 days (versus 4.7±2.2 days in the placebo group, p=0.022), symptoms from the nose/throat and chest – 4.3±2.0 days (versus 5.0±2.3 days in the placebo group; p=0.024).

The total disease severity index decreased more significantly after 5 days of treatment with the drug Ergoferon^®, compared with placebo therapy (p=0.0201). According to the area under the curve (AUC) analysis for the total symptom indices, the severity of ARVI in the Ergoferon^® group was significantly less (p=0.046). At the end of 5 days of treatment with the drug Ergoferon^®, the proportion of patients with recovery from ARVI was 85% (versus 69.0% in the placebo group; p=0.009). A milder course of ARVI in children of the Ergoferon^® group, including a significantly lower severity of fever, was noted with a significantly lower number of antipyretic doses (p=0.0037). Over 14 days of treatment and observation, 1 patient in the Ergoferon^® group had 1 complication (acute adenoiditis), for which an antibiotic was prescribed, which was significantly less frequent than in the placebo group (p=0.0001). Against the background of placebo therapy, antibiotics were required for 19 patients (obstructive bronchitis, n=5; acute otitis, n=3; acute tonsillopharyngitis, n=2; acute adenoiditis, n=8; lymphadenitis, n=1).

The results of an international multicenter double-blind placebo-controlled randomized clinical study of the efficacy and safety of the use of the drug Ergoferon^® showed that the drug Ergoferon^® is an effective and safe drug in the treatment of intestinal infections of viral etiology in children.

The results of the Per Protocol (PP) sample are presented in square brackets.

The average duration of diarrhea in patients of the Ergoferon^® group was 43.4±28.2 [43.0±27.3] hours (versus 54.7±28.3 [57.6±25.5] hours in children of the placebo group), 95% confidence interval – 37.9-49.0 [36.9-49.0] (versus 49.0-60.5 [51.6-63.6] hours), the difference between the groups was 11.3±28.3 [14.6±26.5] hours, respectively (p=0.004 [p=0.0009]). Thus, the use of the drug Ergoferon^® in addition to basic therapy leads to a significant reduction in the duration of diarrhea. The therapeutic effect obtained corresponds to the planned one, which provides for a difference between the groups of at least 12 hours in favor of the drug Ergoferon^® with a standard deviation of at least 36 hours according to the PP analysis, taking into account conservative criteria (α of p=0.0054). The duration of the vomiting period during treatment with the drug Ergoferon^® was 44.6±39.9 [40.8±26.8] hours (versus 57.9±39.7 [55.8±24.2] hours in the placebo group). The difference between the groups was 13.4±28.7 [15.0±25.5] hours (p=0.0044 [p=0.0032]). The average duration of the disease in patients of the Ergoferon^® group was 40.8±28.1 [40.9±28.4] hours (versus 53.0±28.6 [55.8±25.8] hours in patients of the placebo group). Thus, treatment with the drug Ergoferon^® leads to a significant reduction in the duration of the disease – by 12.2±28.3 [14.9±27.2] hours, compared with placebo therapy (p=0.0039 [p=0.0016]). The proportion of patients with clinical recovery 48 hours after the start of treatment in the PP sample of the Ergoferon^® group was 63.0% (versus 42.3% in the placebo group, p=0.0432), after 72 hours – 86.4% (versus 70.4% in the placebo group, p=0.0432).

According to the PP analysis, not a single case of worsening of the disease or nosocomial infection was registered (versus 2 episodes in the placebo group).

The results of a multicenter double-blind placebo-controlled randomized clinical study of the efficacy and safety of the drug Ergoferon^® showed that the drug Ergoferon^® is an effective and safe drug as a means of non-specific prevention of COVID-19 in persons vaccinated against the new coronavirus infection.

The results of the analysis demonstrated a statistically significant superiority of the investigational drug Ergoferon^® in preventing the development of COVID-19 during the vaccination process, compared with placebo therapy (p=0.0046 [p=0.0041]). After the introduction of component I of the “Gam-COVID-Vac” vaccine, taking the drug Ergoferon^® reduces the risk of SARS-CoV-2 infection in vaccinated individuals by more than 3 times over 5 weeks of the vaccination and post-vaccination periods.

During the conducted clinical studies, the safety of the drug Ergoferon^® was confirmed. Treatment did not affect the patients’ vital functions. Laboratory monitoring did not reveal pathological deviations in biochemical markers, blood and urine tests that had a reliable connection with the intake of the investigational drug. The frequency of all adverse events during treatment with the drug Ergoferon^® did not differ from the frequency of adverse events when prescribing placebo.

No data were obtained on the interaction of the drug Ergoferon^® with drugs used as concomitant therapy, including antipyretics and non-steroidal anti-inflammatory drugs, expectorants, bronchodilators, antihypertensive drugs (ACE inhibitors, angiotensin receptor antagonists, beta-blockers, calcium channel antagonists), diuretics, statins, drugs for the treatment of thyroid diseases. Simultaneous administration of these drugs with the drug Ergoferon^® did not lead to the development of pharmacological incompatibility reactions, antagonistic or mutually enhancing effects. In addition, no cases of interaction of the drug Ergoferon^® with drugs used to treat intestinal infections, including adsorbent intestinal drugs, antidiarrheal microorganisms, minerals, oral solutions, plasma-substituting and perfusion solutions and gastrointestinal motility stimulants, were registered.

Preclinical safety data

Preclinical safety studies on sexually mature and immature animals, including studies of acute and chronic toxicity, genotoxicity, reproductive toxicity, immunotoxicity, as well as sensitizing and local irritant properties, did not reveal the presence of toxic or potentially hazardous effects of the drug Ergoferon^® in humans.

Pharmacokinetics

Pharmacokinetic studies are impossible due to the complex composition of the drug.

Indications

• Treatment of influenza and acute respiratory viral infections (ARVI) in adults and children aged 6 months and older;
• Treatment of acute intestinal infections of viral etiology (AII) in adults and children aged 6 months and older;
• Non-specific prevention of COVID-19 during the vaccination period between the administration of the first and second components of the vaccine against the new coronavirus infection in adults.

ICD codes

Dosage Regimen

Tablets

The score line is not intended for dividing the tablet into parts.

The recommended dose for adults is 1 tablet per dose.

Treatment of Influenza, ARVI, and ARI

Adults and children from 6 months of age. On the first day of treatment, take 8 tablets according to the following schedule: 1 tablet every 30 minutes in the first 2 hours (5 tablets total in 2 hours), then, on the same day, take 1 more tablet 3 times at equal intervals.

On the 2nd day and thereafter, take 1 tablet 3 times a day until complete recovery.

If necessary, the drug can be combined with other antiviral and symptomatic agents.

The safety and efficacy of Ergoferon^® in children aged 0 to 6 months have not been established to date. Data are unavailable.

Non-specific prophylaxis of COVID-19 during the vaccination period between the administration of the first and second components of the vaccine against the novel coronavirus infection in adults

Adults. 1 tablet per dose, 2 times a day. The duration of administration is up to 3 weeks.

The safety and efficacy of Ergoferon^® in children aged 0 to 18 years have not been established to date. Data are unavailable.

Method of Administration

The drug is taken orally, not during meals. The tablet should be held in the mouth, without swallowing, until completely dissolved.

When prescribing the drug to young children (from 6 months to 3 years), it is recommended to dissolve the tablet in a small amount (1 tablespoon) of boiled water at room temperature.

Solution

Take orally according to a special schedule.

If necessary, it can be combined with other antiviral and symptomatic agents.

Adverse Reactions

Possible reactions of increased individual sensitivity to the components of the drug.

If any adverse reactions mentioned in the instructions occur, or if they worsen, or if any other adverse reactions not mentioned in the instructions appear, a doctor should be informed.

Contraindications

• Hypersensitivity to the active substances or to any of the excipients included in the drug.

Use in Pregnancy and Lactation

The safety of using Ergoferon^® during pregnancy and lactation has not been studied.

During pregnancy and breastfeeding, the drug should be used only if the intended benefit to the mother outweighs the potential risk to the fetus and child. The “benefit-risk” ratio is determined by the attending physician.

Pediatric Use

The use of the drug is contraindicated in children under 6 months of age.

Special Precautions

Excipients

The drug contains lactose; therefore, patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Effect on the ability to drive vehicles and machinery

Ergoferon^® does not affect the ability to drive vehicles and other potentially dangerous machinery.

Overdose

Symptoms: dyspeptic symptoms are possible in case of overdose, due to the excipients included in the drug.

Treatment: discontinuation of the drug, administration of symptomatic therapy, such as oral rehydration.

Drug Interactions

No cases of incompatibility with other medicinal products have been reported to date.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.