Imunovir-health

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IMUNOVIR-ZDOROVYE (IMUNOVIR-ZDOROVYE)

Composition:

Active substance: inosine pranobex;

1 ml of the preparation contains 50 mg of inosine pranobex;

Excipients: sucrose; methylparaben (E 218); propylparaben (E 216); sodium hydroxide; citric acid; purified water; lemon flavoring.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear liquid, ranging from colorless to yellow, with a slight lemon odor.

Pharmacotherapeutic group. Antiviral agents for systemic use. Other antiviral agents. ATC code J05A X05.

Pharmacological Properties.

Pharmacodynamics.

Immunovir-Health contains methisoprinol (inosine pranobex), a synthetic purine derivative that has immunomodulatory and antiviral properties resulting from pronounced stimulation of the host's immune response in vivo by the drug.

Clinical studies have shown that inosine pranobex normalizes deficiencies or dysfunctions of cellular immunity by inducing Th1-type responses, leading to maturation and differentiation of T-lymphocytes and potentiation of lymphoproliferative response in mitogen- or antigen-activated cells. Furthermore, the drug has been shown to regulate cytotoxic mechanisms of T-lymphocytes and NK cells, the function of CD8+ suppressor lymphocytes and CD4+ helper lymphocytes, and also increases levels of IgG and surface complement markers. In vitro studies demonstrated that inosine pranobex enhances production of cytokines IL-1 and IL-2, while simultaneously increasing IL-2 receptor expression. In vivo studies showed significantly increased secretion of endogenous gamma-interferon (IFN-γ) and reduced secretion of IL-4. It has also been shown that the drug enhances chemotaxis and phagocytosis by neutrophils, monocytes, and macrophages.

In vivo studies revealed that inosine pranobex activates reduced synthesis of lymphocyte protein mRNA and improves translational efficiency, while simultaneously inhibiting viral RNA synthesis through the following mechanisms (their involvement requires further investigation):

1. Incorporation of orotic acid bound to inosine into polyribosomes.
2. Inhibition of polyadenylic acid attachment to viral messenger RNA.
3. Restructuring of mesothelial protein complexes involved in signal transduction via the specific T-cell receptor (TcR) in lymphocytic intramembrane microdomains (IMP), nearly tripling their density.

Inosine pranobex inhibits cGMP-phosphodiesterase in vitro, but only at high concentrations; this effect does not occur at drug concentrations that provide immunopharmacological activity in vivo.

Pharmacokinetics.

Absorption. After oral administration in humans, methisoprinol is rapidly and completely absorbed (≥ 90%) from the gastrointestinal tract into the bloodstream. Similarly, 94–100% of the dose of its components, DIP (N,N-dimethylamino-2-propanol) and PABA (para-aminobenzoic acid), administered intravenously, is recovered in urine after oral administration in rhesus macaques.

Distribution. In animal studies, radiolabeled material was detected in the following organs (in descending order of specific activity): kidneys, lungs, liver, heart, spleen, testes, pancreas, brain, and skeletal muscles.

Metabolism. After oral administration of 1 g of radiolabeled methisoprinol in humans, plasma concentrations of DIP and PABA reached 3.7 µg/mL (at 2 hours) and 9.4 µg/mL (at 1 hour), respectively.

Dose-tolerance studies have shown that peak post-dose increase in uric acid concentration—used as an indicator of methisoprinol metabolism—follows a nonlinear pattern and may vary within ±10% over 1–3 hours.

Elimination. Daily urinary excretion of PABA and its main metabolite at steady state with a dosage of 4 g/day amounted to approximately 85% of the administered dose. 95% of radioactive DIP was recovered in urine as unchanged substance and its metabolite, the N-oxide. The elimination half-life is 3.5 hours for DIP and 50 minutes for PABA. The main metabolites of methisoprinol in humans are the N-oxide for DIP and the ortho-acylglucuronide for PABA. Since the inosine molecule is metabolized through purine biodegradation into uric acid, radiolabeled inosine pranobex studies in humans are non-informative. In animals, up to 70% of administered inosine pranobex may be excreted in urine as uric acid after oral administration of the tablet form, with the remainder excreted as usual metabolites—xanthine and hypoxanthine.

Bioavailability (AUC). Urinary recovery of PABA and its metabolite at steady state was > 90% of the expected value from solution. Recovery of DIP and its metabolite was > 76%. Plasma AUC values for DIP were ≥ 88%, and for PABA ≥ 77%.

Clinical characteristics.

Indications.

The medicinal product is indicated for the treatment of reduced or dysfunctional cellular immunity and for the treatment of clinical symptoms associated with the following conditions:

• Primary and secondary viral respiratory infections.
• Viral infections caused by herpes simplex virus types 1 and 2, varicella-zoster virus (VZV), cytomegalovirus (CMV), or Epstein-Barr virus (EBV).
• Genital warts (condyloma acuminata) — external lesions (excluding meatal and perianal localization) as monotherapy or as an adjunct to conventional local or surgical treatment.
• Mucosal infections, subclinical vulvovaginal infections, or infections caused by human papillomavirus (HPV) associated with the endocervix.
• Viral hepatitis.
• Complicated measles or measles with complications.
• Subacute sclerosing panencephalitis (SSPE).

Contraindications.

The medicinal product must not be used:

• in patients with known hypersensitivity to the active substance or to any of the excipients of the product;
• in patients during an acute attack of gout;
• in patients with elevated blood uric acid levels (hyperuricemia).

Interaction with other medicinal products and other forms of interaction.

Use with caution in patients receiving xanthine oxidase inhibitors (e.g., allopurinol) and agents that enhance urinary excretion of uric acid, including thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone, indapamide) and loop diuretics (furosemide, torasemide, ethacrynic acid).

The medicinal product should not be taken during immunosuppressive therapy, as concomitant use of immunosuppressants may affect its expected therapeutic effect due to specific pharmacokinetic mechanisms (use is possible only after completion of immunosuppressive therapy).

Concomitant administration of the medicinal product with zidovudine (azidothymidine or AZT) enhances the formation of zidovudine nucleotides through different mechanisms, resulting from increased bioavailability of zidovudine in blood plasma and enhanced intracellular phosphorylation in blood monocytes. This leads to potentiation of zidovudine effects under the influence of the product.

Special precautions for use.

The medicinal product may cause a transient increase in serum and urinary uric acid levels, but these levels usually remain within normal limits (upper limit being 8 mg/dL or 0.42 mmol/L, respectively), particularly in elderly patients and younger men. The increase in uric acid levels results from the catabolic metabolism of the active ingredient's inosine component into uric acid and is not due to changes in enzymatic activity or renal clearance caused by the drug. Therefore, inosine pranobex should be used with caution in patients with a history of gout, hyperuricemia, urolithiasis, or renal dysfunction. Patients should closely monitor their uric acid levels during treatment.

Severe hypersensitivity reactions (e.g., urticaria, angioneurotic edema, anaphylaxis) may occur in some patients. If such reactions occur, the drug must be discontinued immediately.

Renal stones may develop during prolonged treatment. In all patients undergoing long-term therapy, regular monitoring of serum and urinary uric acid levels, liver function, blood parameters, and renal function is recommended.

Excipients.

The medicinal product contains sucrose, which may be harmful to teeth. Each 1 ml of syrup contains 650 mg of sucruise. This should be taken into account by patients with diabetes mellitus. If a patient has known sugar intolerances, medical advice should be sought before taking this medicinal product.

The medicinal product contains methylparaben (E 218) and propylparaben (E 216), which may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

The effects of inosine on fetal development and human fertility have not been studied. It is unknown whether inosine passes into breast milk. The drug should not be used during pregnancy or breastfeeding unless the physician considers the potential benefit to outweigh the potential risks.

Ability to influence reaction rate while driving or operating machinery.

The medicinal product has no effect or negligible effect on the ability to drive or operate machinery.

Dosage and Administration.

This medicinal product is intended for oral use only.

The daily dose should be divided evenly into doses taken throughout the day.

Dosage.

Dosage is determined individually by a physician, depending on the patient's body weight and course of the disease.

Adults, including elderly patients.

The recommended daily dose is 50 mg/kg body weight per day (i.e., 1 mL/kg), usually 3 g (or 60 mL) of syrup, divided into 3–4 doses per day. The maximum daily dose is 4 g.

Children.

The recommended daily dose is 50 mg/kg body weight (1 mL/kg) per day, evenly divided into 3–4 doses throughout the day according to the following table:

*To measure the dose, use the dosing cup provided in the package.

Duration of treatment.

Acute conditions.

For diseases with a short course, treatment lasts 5–14 days. After symptoms have subsided, treatment should be continued for another 1–2 days or longer, as decided by the physician.

Viral diseases with prolonged course.

Treatment should be continued for 1–2 weeks after reduction in symptom severity, or longer, as decided by the physician.

Recurrent diseases.

Initially, the same recommendations apply as for acute conditions. During maintenance therapy, the dose may be reduced to 500–1000 mg/day. At the first signs of recurrence, the daily dose recommended for acute conditions should be resumed and continued for 1–2 days after symptom resolution. The treatment course may be repeated several times as needed, depending on the patient's condition and at the physician's recommendation.

Chronic diseases.

The recommended dose is 50 mg/kg body weight according to the following regimens:

Asymptomatic conditions: administer for 30 days with a 60-day break;

Mild symptoms: administer for 60 days with a 30-day break;

Severe symptoms: administer for 90 days with a 30-day break.

The treatment course should be repeated as often as necessary, with continuous monitoring of the patient's condition and indications for continuing therapy.

Dosing for special indications.

External genital condyloma (condyloma acuminata) or endocervical HPV infections:

Administer 3 g/day for 14–28 days as monotherapy or as an adjunct to local therapy or surgical treatment according to the following regimens:

a) for treatment of low-risk patients (patients without immunodeficiency or with low risk of recurrence), the drug is administered continuously for 14–28 days followed by a two-month treatment-free period during which lesions decrease or resolve;

or

b) for treatment of high-risk patients * (patients with immunodeficiency or high risk of recurrence), the drug is administered 5 days per week for 2 consecutive weeks each month, or 5 days per week every other week, over a 3-month period.

If necessary, treatment courses may be repeated several times.

*The "high-risk" profile for recurrence or cervical dysplasia in patients with genital HPV infection resembles that of other conditions and includes the following diseases and conditions:

• Genital HPV infection lasting more than 2 years or with a history of 3 or more recurrences.
• Immune suppression due to:
  • recurrent or chronic infections;
  • other sexually transmitted infections (STIs);
  • chemotherapy for oncological diseases;
  • chronic alcoholism.
• Poorly controlled diabetes.
• Atopy.
• Long-term use of oral contraceptives (2 years or more).
• Erythrocyte folate level below 660 nmol/L.
• Multiple sexual partners or change of regular sexual partner.
• Frequent vaginal intercourse (≥ 2–6 times per week).
• Anal intercourse.
• Negative history of skin warts in childhood.
• Age over 20 years.
• Smoking.

Subacute sclerosing panencephalitis:

The daily dose is 100 mg/kg body weight per day, with a maximum dose of 60–80 mL/day. Treatment is long-term and continuous, with regular monitoring of the patient's health status and periodic reassessment of further therapy. The recommended daily dose may be increased, especially in severe cases.

Children. See section "Method of administration and dosage."

Overdose.

No cases of overdose have been reported. Based on toxicological studies in animals, serious adverse reactions are unlikely except for increased uric acid levels in the body. Treatment is limited to symptomatic and supportive measures.

Adverse reactions.

The only consistent adverse reaction during treatment with inosine pranobex in adults and children is a temporary increase (usually within normal limits) in serum and urinary uric acid levels, which returns to normal within a few days after discontinuation of the drug.

The frequency of adverse reactions is defined as follows:

Reporting of suspected adverse reactions

Reporting adverse reactions after the medicinal product has been registered is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

The shelf life of the medicinal product after opening the bottle is no more than 6 months.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Do not refrigerate.

Keep out of reach and sight of children.

Packaging.

200 ml in a glass bottle; 1 bottle with a measuring cup in a cardboard box.

100 ml or 200 ml in a polymer bottle; 1 bottle with a measuring cup in a cardboard box.

Category of supply. By prescription only.

Manufacturer.

Limited Liability Company "Pharmaceutical Company "Zdorovya".

Manufacturer's address and location of its business activity.

22, Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.