NOVIRIN FORTE

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOVIRIN FORTE (NOVIRIN FORTE)

Composition:

Active substance: inosine pranobex;

1 tablet contains 1,000 mg of inosine pranobex;

Excipients: potato starch, povidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics:

1,000 mg tablets: elongated tablets with a biconvex surface, scored on both sides, color from almost white to yellowish-white.

Pharmacotherapeutic group. Direct-acting antiviral agents. ATC code J05AX05.

Pharmacological Properties.

Pharmacodynamics.

The active substance – inosine pranobex (a molecular complex of inosine : p-acetamidobenzoic acid : N,N-dimethylamino-2-propanol in a ratio of 1:3:3) exerts direct antiviral and immunomodulating effects. The direct antiviral action is due to binding to ribosomes of virus-infected cells, which slows down viral mRNA synthesis (disruption of transcription and translation), leading to inhibition of replication of both RNA- and DNA-genome viruses. The indirect antiviral effect is explained by potent induction of interferon production.

The immunomodulating effect is attributed to its influence on T-lymphocytes (stimulation of cytokine synthesis) and enhancement of macrophage phagocytic activity. Under the influence of the drug, differentiation of pre-T-lymphocytes is enhanced, mitogen-induced proliferation of T- and B-lymphocytes is stimulated, functional activity of T-lymphocytes is increased, including their ability to produce lymphokines, and the ratio between T-helper and T-suppressor subpopulations is normalized (immunoregulatory CD4/CD8 index is restored). The medicinal product significantly enhances interleukin-2 production by lymphocytes and promotes expression of receptors for this interleukin on lymphoid cells. It also stimulates natural killer (NK) cell activity, even in healthy individuals, and enhances macrophage activity in phagocytosis, antigen processing, and presentation, thereby increasing the number of antibody-producing cells in the body as early as the first days of treatment.

It also stimulates synthesis of interleukin-1, microbial killing activity, expression of membrane receptors, and responsiveness to lymphokines and chemotactic factors. In herpes virus infections, production of specific anti-herpetic antibodies is significantly accelerated, while clinical symptoms and frequency of recurrences are reduced.

The drug also prevents post-viral weakening of cellular RNA and protein synthesis in previously infected cells, which is particularly important for cells involved in immune defense mechanisms. As a result of this comprehensive action, viral load on the body is reduced, immune system function is normalized, endogenous interferon synthesis is significantly enhanced, promoting resistance to infectious diseases and rapid localization of infection foci if they occur.

Pharmacokinetics.

The drug has high bioavailability. After oral administration, it is rapidly absorbed, with maximum plasma concentration of inosine reached within 1 hour. Pharmacological effects manifest approximately 30 minutes after administration and last up to 6 hours.

Inosine is metabolized through a pathway typical for purine nucleosides, resulting in the formation of uric acid. Other components are excreted by the kidneys as glucuronide and oxidized derivatives, as well as in unchanged form. No accumulation in the body has been observed. Complete elimination of the drug and its metabolites occurs within 48 hours.

Clinical characteristics.

Indications.

• Viral infections in patients with normal and reduced immune status: influenza, parainfluenza, acute respiratory viral infections, viral bronchitis, rhinovirus and adenovirus infections; epidemic parotitis, measles;
• diseases caused by: herpes simplex virus Herpes simplex types I or II (herpes labialis, facial skin, oral mucosa, hand skin, ophthalmic herpes); subacute sclerosing panencephalitis; genital herpes; Varicella zoster virus (chickenpox and herpes zoster, including recurrent forms in immunocompromised patients); Epstein-Barr virus (infectious mononucleosis); cytomegalovirus; human papillomavirus; acute and chronic viral hepatitis B;
• chronic recurrent respiratory tract and urogenital infections in patients with impaired immunity (chlamydia and other diseases caused by intracellular pathogens).

Contraindications.

Hypersensitivity to inosine pranobex and other components of the drug; gout, urolithiasis, severe renal insufficiency stage III, hyperuricemia.

Interaction with other medicinal products and other forms of interaction.

The drug should not be taken simultaneously with immunosuppressants. 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).

When used concomitantly with zidovudine, increased nucleotide formation occurs due to increased bioavailability of zidovudine in blood plasma and enhanced intracellular phosphorylation in human blood monocytes.

Special precautions for use.

It should be remembered that Novirin Forte, like other antiviral agents, is most effective in acute viral infections when treatment is initiated at an early stage of the disease (preferably within the first 24 hours). The medicinal product may be used both as monotherapy and as part of combination therapy with antibiotics, antiviral agents, and other etiotropic treatments.

The active substance of the medicinal product is metabolized to uric acid and may cause a significant increase in its concentration in urine. Therefore, Novirin Forte should be used with caution in patients with a history of gout or hyperuricemia, urolithiasis, or renal insufficiency. When use in such patients is necessary, careful monitoring of uric acid concentration is required. During prolonged treatment (3 months or longer), monthly monitoring of serum and urinary uric acid concentrations, liver function, peripheral blood count, and renal function parameters is advisable.

In some individuals, acute hypersensitivity reactions may occur (angioneurotic edema, anaphylactic shock, urticaria). In such cases, treatment with the medicinal product should be discontinued.

With prolonged use of the medicinal product, there is a risk of developing nephrolithiasis.

Elderly patients. There is no need to adjust the dosage; the medicinal product should be administered at the adult dose. In elderly individuals, increased levels of uric acid in serum and urine are observed more frequently than in middle-aged individuals.

Use during pregnancy or breastfeeding.

Studies on fetal outcomes and fertility impairment in humans are lacking. It is unknown whether inosine pranobex is excreted in breast milk. In the absence of safety data, the medicinal product is not recommended during pregnancy or breastfeeding.

Ability to affect reaction rate while driving or operating machinery.

The effect of the medicinal product on reaction speed during driving or operating machinery has not been studied. However, when making decisions regarding driving or operating machinery, it should be taken into account that the medicinal product may cause dizziness or other adverse reactions affecting the nervous system (see section "Adverse reactions").

Method of Administration and Dosage

The medicinal product should be taken orally, preferably after meals and at regular intervals. If necessary, the tablet may be chewed, crushed, and/or dissolved in a small amount of water immediately before administration. The duration of treatment is determined individually by a physician depending on the nosology, severity of the disease, and frequency of relapses; on average, treatment lasts 5–14 days. If necessary, the course may be repeated after a 7–10-day break. Continuous treatment may last up to 3 months, while treatment with breaks and maintenance doses may continue for up to 6 months.

Recommended Dosages and Administration Schemes of the Medicinal Product

Influenza, parainfluenza, acute respiratory viral infections:

Adults – 1 tablet of 1000 mg 3–4 times daily; children – daily dose calculated at 50 mg/kg body weight administered in 3–4 doses for 5–7 days. If necessary, treatment may be continued or repeated after 7–8 days. For maximum efficacy in acute respiratory viral infections, treatment should be initiated at the first signs of illness or on the first day of disease. The medicinal product should generally be continued for 1–2 days after symptoms have resolved.

Viral bronchitis:

Adults – 1 tablet of 1000 mg 3 times daily; children – daily dose calculated at 50 mg/kg administered in 3–4 doses for 2–4 weeks.

Epidemic parotitis (mumps): daily dose calculated at 70 mg/kg administered in 3–4 doses for 7–10 days.

Measles: daily dose calculated at 100 mg/kg administered in 3–4 doses for 7–14 days.

Recurrent herpesvirus infection types I and II:

Adults – 100 mg/kg daily for 14 days, followed by 50 mg/kg daily for up to 3 months.

Aphthous stomatitis:

Adults – 1 tablet of 1000 mg 4 times daily; children – daily dose calculated at 70 mg/kg administered in 3–4 doses for 6–8 days (acute phase);

then adults – 1 tablet of 1000 mg 3 times daily; children – 50 mg/kg administered in 3–4 doses twice weekly for 6 weeks.

Infectious mononucleosis: daily dose calculated at 50 mg/kg administered in 3–4 doses for 8 days.

Cytomegalovirus infection: daily dose calculated at 50 mg/kg administered in 3–4 doses for 25–30 days.

Herpes zoster and labial herpes:

Adults – 1 tablet of 1000 mg 3–4 times daily; children – daily dose calculated at 50 mg/kg administered in 3–4 doses for 10–14 days (until symptoms resolve).

Genital herpes: during acute phase – 1 tablet of 1000 mg 3 times daily for 5–6 days; during remission – maintenance dose of 1000 mg once daily for up to 6 months.

Subacute sclerosing panencephalitis: daily dose calculated at 50–100 mg/kg administered in 6 doses (every 4 hours) for 8–10 days; after an 8-day break, 1–3 additional courses for mild cases, up to 9 courses for severe cases.

Infections caused by Human papilloma virus (anogenital warts): 1 tablet of 1000 mg 3 times daily for 14–28 days; when combined with cryotherapy or CO2-laser therapy – 1 tablet of 1000 mg 3 times daily for 5 days, 3 courses with 1-month intervals.

Hepatitis B: adults – 1 tablet of 1000 mg 3–4 times daily for 15–30 days; then maintenance dose – 1 tablet of 1000 mg once daily for 2–6 months.

Chronic recurrent respiratory and urogenital tract infections in immunocompromised patients (as part of combination therapy):

Adults – 1 tablet of 1000 mg 3–4 times daily, treatment course from 2 weeks to 3 months; children – daily dose calculated at 50 mg/kg administered in 3–4 doses for 21 days (or 3 courses of 7–10 days with equal intervals).

To restore immune system function and achieve a sustained immunomodulatory effect in immunocompromised patients, the treatment course should last from 3 to 9 weeks.

Elderly patients. The medicinal product can be used at standard adult doses; no dose adjustment is required.

Children. The medicinal product is indicated for children aged 1 year and older.

Overdose.

Cases of overdose have not been reported. Overdose may lead to increased serum and urinary uric acid concentrations. In case of overdose, gastric lavage and symptomatic therapy are indicated.

Side effects.

The medicinal product is generally well tolerated even with long-term use. The most common adverse reaction is a transient and insignificant (usually within normal limits) increase in the concentration of uric acid in blood serum and urine (caused by inosine metabolism), which normalizes within several days after discontinuation of the medicinal product.

Laboratory investigations: increased levels of uric acid in blood, increased levels of uric acid in urine, increased blood urea nitrogen levels, increased transaminase levels, increased alkaline phosphatase levels in blood.

Nervous system disorders: headache, dizziness, increased fatigue, malaise, sleep disturbances.

Gastrointestinal disorders: nausea, vomiting, epigastric pain, diarrhea, constipation, loss of appetite.

Skin and subcutaneous tissue disorders: pruritus, skin rashes, urticaria.

Immune system disorders: hypersensitivity reactions (including angioedema).

Psychiatric disorders: restlessness.

Hepatobiliary disorders: increased levels of transaminases, alkaline phosphatase, or blood urea nitrogen in blood.

Musculoskeletal and connective tissue disorders: joint pain.

Renal and urinary disorders: polyuria (increased urine volume).

During post-marketing surveillance, the following adverse reactions have been reported, for which the frequency cannot be estimated from the available data:

Gastrointestinal disorders: abdominal pain (in the upper abdomen);

Immune system disorders: anaphylactic reactions, anaphylactic shock, angioedema, hypersensitivity, urticaria;

Skin and subcutaneous tissue disorders: erythema.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

Tablets of 1000 mg: 10 tablets in a blister; 3 or 4 blisters in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of business activity.

38, Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua