Novirin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOVIRIN

Composition:

Active substance: inosine pranobex;

1 tablet contains 500 mg of inosine pranobex;

Excipients: potato starch, povidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics:

500 mg tablets: round, biconvex tablets with a score line, nearly white to yellowish-white in color.

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 immunomodulatory effects. The direct antiviral action is due to binding to ribosomes of virus-infected cells, which slows down the synthesis of viral mRNA (disruption of transcription and translation), resulting in suppression of replication of both RNA- and DNA-genome viruses. The indirect antiviral effect is explained by potent induction of interferon production.

The immunomodulatory effect is mediated by 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 increases, including their ability to produce lymphokines, and the ratio between T-helper and T-suppressor subpopulations is normalized (immunoregulatory index CD4/CD8 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 antigen presentation, leading to an increase in antibody-producing cells in the body as early as the first days of treatment.

The drug also stimulates synthesis of interleukin-1, microbial killing activity, expression of membrane receptors, and the ability to respond 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 medicinal product 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, contributing to increased resistance to infectious diseases and rapid localization of infection foci if they occur.

Pharmacokinetics

The medicinal product has high bioavailability and is rapidly absorbed after oral administration. Maximum plasma concentration of inosine is reached within 1 hour; pharmacological effects appear approximately 30 minutes after administration and last up to 6 hours.

Inosine is metabolized via a pathway typical for purine nucleosides, forming uric acid. Other components are excreted by the kidneys as glucuronide and oxidized derivatives, as well as unchanged. 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 reduced immune status, in case of recurrent upper respiratory tract infections
• Treatment of herpes labialis and facial herpes caused by herpes simplex virus (Herpes simplex)

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

The medicinal product should not be taken simultaneously with immunosuppressants. Use with caution in patients taking 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 plasma bioavailability of zidovudine and enhanced intracellular phosphorylation in human blood monocytes.

Special precautions for use

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

The active ingredient of the medicinal product is metabolized to uric acid and may cause a significant increase in its concentration in urine. Therefore, Novirin should be used with caution in patients with a history of gout or hyperuricemia, urolithiasis, or renal insufficiency. When use of the medicinal product is necessary in such patients, 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.

Prolonged use of the medicinal product carries a risk of nephrolithiasis development.

Elderly patients. There is no need to adjust the dosage; the medicinal product should be administered at the adult dose. Elevated levels of uric acid in serum and urine are observed more frequently in elderly individuals compared to those of middle age.

Use during pregnancy or breastfeeding.

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

Ability to influence reaction speed when driving or operating machinery.

The effect of the medicinal product on reaction speed when driving or operating machinery has not been studied. However, when making decisions about 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").

Administration and Dosage

The medicinal product should be taken orally, preferably after meals and at regular intervals. If necessary, the tablet can 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, and the medication should be continued for another 1–2 days after symptoms have disappeared.

Recommended dosage and administration regimens of the medicinal product

Viral infections in patients with reduced immune status in case of recurrent upper respiratory tract infections:

Adults – 2 tablets of 500 mg 3–4 times daily; Children – daily dose calculated at 50 mg/kg body weight given in 3–4 divided doses.

Diseases caused by Herpes simplex virus types I or II (herpes labialis, facial skin, oral mucosa, hand skin, ophthalmic herpes):

Adults – 2 tablets of 500 mg 3–4 times daily; Children – daily dose calculated at 50 mg/kg body weight given in 3–4 divided doses.

For maximum treatment efficacy, therapy should be initiated at the first signs of disease or during the first day of illness.

Elderly patients. The medicinal product can be used at the standard adult dosage; dose adjustment is not required.

Children. The medicinal product can be administered to 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 during prolonged use. The most common adverse reaction is a short-term and insignificant (usually within normal limits) increase in serum and urinary uric acid concentration (caused by inosine metabolism), which normalizes within several days after discontinuation of the medicinal product.

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

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

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

Skin and subcutaneous tissue: itching, skin rash, urticaria.

Immune system: hypersensitivity reactions (including angioedema).

Psychiatric disorders: irritability.

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

Musculoskeletal and connective tissue: joint pain.

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

During post-marketing surveillance, the following adverse reactions have been reported; their frequency cannot be determined based on available data:

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

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

Skin and subcutaneous tissue: 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.

10 tablets in a blister; 2 blisters per carton.

10 tablets in a blister; 4 blisters per carton.

Availability. Over-the-counter.

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