INOSINE PRANOBEX

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT INOSINE PRANOBEX (INOSINE PRANOBEX)

Composition:

Active substance: inosine pranobex;

One tablet contains 500 mg of inosine pranobex;

Excipients: maize starch, povidone K-25, magnesium stearate, mannitol (E 421).

Pharmaceutical form. Tablets.

Main physicochemical characteristics: round tablets, from nearly white to yellowish-white, with a biconvex surface, with a slight specific odor.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antiviral agents for systemic use. Direct-acting antiviral agents.
ATC code J05A X05.

Pharmacological Properties

Pharmacodynamics

INOZIN PRANOBEX is an antiviral agent with immunomodulatory properties. The drug eliminates deficiency or dysfunction of cellular immunity by inducing maturation and differentiation of T-lymphocytes and T1-helper cells, enhancing the induction of lymphoproliferative response in mitogen- or antigen-activated cells. Inosine pranobex modulates cytotoxic activity of T-lymphocytes and natural killer cells, regulates function of T8-suppressor and T4-helper cells, and increases levels of immunoglobulin G and complement surface markers. Inosine pranobex enhances synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), regulates expression of IL-2 receptors. Inosine pranobex significantly increases secretion of endogenous gamma-interferon and reduces formation of interleukin-4 in the body. Inosine pranobex enhances activity of neutrophil granulocytes, chemotaxis, and phagocytosis by monocytes and macrophages. Inosine pranobex inhibits viral replication by incorporating inosine acylate into polyribosomes of virus-infected cells and by inhibiting adenylic acid attachment to viral mRNA.

Pharmacokinetics

After oral administration of a 1.5 g dose, maximum plasma concentration of inosine pranobex is reached within 1 hour and amounts to 600 μg/mL. Inosine pranobex is metabolized in the liver to form uric acid. The elimination half-life of 4-(acetylamino)benzoate is 50 minutes, and that of 1-(dimethylamino)-2-propanol is 3.5 hours. The drug is excreted renally in the form of metabolites.

Clinical characteristics.

Indications.

INOZIN PRANOBEX is indicated for the treatment of decreased or dysfunctional cell-mediated immunity and clinical symptoms associated with such conditions:

• viral respiratory infections, primary and secondary immunodeficiency states;
• infections caused by herpesviruses: herpes simplex virus types 1 and 2, varicella-zoster virus; infections caused by cytomegalovirus and Epstein-Barr virus;
• genital warts (anogenital condylomata acuminata) — external lesions (excluding perianal areas and areas within the anal canal) — as monotherapy or as adjunctive therapy in combination with local or surgical treatment;
• papillomavirus infections of the skin and mucous membranes, vulva and vagina (subclinical) or cervix;
• viral hepatitis;
• severe or complicated measles;
• subacute sclerosing panencephalitis.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product, acute gout, hyperuricemia.

Interaction with other medicinal products and other forms of interaction.

INOZIN PRANOBEX should be administered with caution in combination with xanthine oxidase inhibitors (e.g., allopurinol) or agents promoting uric acid excretion, including diuretics, particularly thiazide diuretics (such as hydrochlorothiazide, chlorthalidone, indapamide) or loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

INOZIN PRANOBEX may be used after, but not simultaneously with immunosuppressants, due to a possible pharmacokinetic impact on desired therapeutic effects.

When administered concomitantly with zidovudine (azidothymidine), increased formation of the nucleotide azidothymidine occurs via multiple mechanisms, including increased plasma bioavailability of zidovudine and enhanced intracellular phosphorylation in human blood monocytes. This results in potentiation of the effect of zidovudine.

Special precautions for use.

During treatment with inosine pranobex, a temporary increase in serum and urinary uric acid levels may occur, particularly in men and elderly individuals. However, these values usually remain within normal limits (up to 8 mg/dL or 0.420 mmol/L, respectively). The increase in uric acid levels is due to the catabolic metabolism of inosine in humans. This occurs not due to a drug-induced fundamental alteration in enzymatic function or renal clearance.

Therefore, the medicinal product should be used with particular caution in patients with a history of gout, hyperuricemia, urolithiasis, or impaired renal function. During treatment, uric acid levels should be monitored in these patients.

Acute hypersensitivity reactions (e.g., angioneurotic edema, anaphylactic shock, urticaria) may occur in some individuals. In such cases, inosine pranobex therapy should be discontinued.

With prolonged use of the drug, there is a risk of developing kidney and gallbladder stones.

During long-term treatment, serum and/or urinary uric acid levels, liver function, blood count, and renal function should be regularly monitored in all patients.

Use during pregnancy or breastfeeding.

Pregnancy. Studies on the risk of fetal abnormalities or impaired fertility in humans have not been conducted. INOSINE PRANOBEX should not be used during pregnancy unless the physician decides that the potential benefit outweighs the potential risk.

Breastfeeding. It is unknown whether inosine pranobex is excreted in human breast milk. Risk to infants cannot be excluded. Breastfeeding should be discontinued during treatment.

Fertility. There are no data on the effect of the medicinal product on human fertility. Animal studies have shown no effect on fertility.

Ability to influence reaction speed when driving or operating machinery.

INOSINE PRANOBEX has no effect or has a negligible effect on the ability to drive or operate machinery.

Administration and Dosage

The medicinal product should be administered orally. The daily dose depends on body weight and severity of the disease; the dose should be evenly distributed throughout the day. To facilitate swallowing, the tablet may be crushed and dissolved in a small amount of liquid before administration.

Adults and elderly patients: The recommended dose is 50 mg/kg body weight (1 tablet per 10 kg body weight), usually 3 g/day (6 tablets), with a maximum dose of 4 g/day (8 tablets); administered orally in 3–4 divided doses throughout the day.

Children from 1 year of age: The dose is 50 mg/kg body weight per day (1 tablet per 10 kg body weight for children with body weight up to 20 kg; for children with body weight above 20 kg, administer the adult dose).

Treatment Duration

Acute diseases: For conditions with a short course, treatment duration is 5 to 14 days. After symptom severity decreases, treatment should be continued for another 1–2 days or longer, depending on the physician's decision.

Viral diseases with prolonged course: Treatment should be continued for 1–2 weeks after symptom severity decreases, or longer, based on the physician's decision.

Recurrent diseases: Initial treatment should follow the same recommendations as for acute diseases. During maintenance therapy, the dose may be reduced to 500–1000 mg (1–2 tablets) per day. At the first signs of recurrence, the daily dose recommended for acute diseases should be resumed and continued for 1–2 days after symptoms disappear. Treatment courses may be repeated several times if necessary, according to the physician’s assessment of the clinical condition.

Chronic diseases: The drug should be prescribed at a daily dose of 50 mg/kg body weight according to the following regimens:

• asymptomatic conditions: administer for 30 days with a 60-day break;
• conditions with moderate symptoms: administer for 60 days with a 30-day break;
• conditions with severe symptoms: administer for 90 days with a 30-day break.

This treatment may be repeated if necessary; the patient's condition should be monitored as in recurrent conditions.

Dosage for Special Indications

External genital warts (condylomata acuminata) or cervical canal papillomavirus infection: Take 2 tablets three times daily (3 g) as monotherapy or as an adjunct to local therapy or surgical treatment, according to the following regimens:

• low-risk patients (patients with normal immunity or low risk of recurrence): administer the medicinal product continuously for 14–28 days within a 3-month period, followed by a 2-month treatment break; continue until lesions decrease or disappear;
• high-risk patients * (patients with immunodeficiency or high risk of recurrence): within a 3-month period, administer the drug 5 days per week for 2 consecutive weeks per month, or 5 days per week every other week.

This treatment may be repeated several times as needed.

Subacute sclerosing panencephalitis: The daily dose is 100 mg/kg body weight, with a maximum dose of 3–4 g/day. Treatment is long-term and continuous, with regular assessment of the patient's condition and the need for continued therapy.

* High-risk factors for recurrence or cervical dysplasia in patients with genital papillomavirus infection, as in other similar conditions, include:

• genital papillomavirus infection lasting more than 2 years or with 3 or more recurrences in history;

• immunodeficiency due to:

• recurrent or chronic infections;

• sexually transmitted diseases;

• anticancer chemotherapy;

• chronic alcoholism;

• poorly controlled diabetes mellitus;

• atopy (hereditary predisposition to hypersensitivity);

• prolonged use of contraceptives (more than 2 years);

• erythrocyte folate levels ≤660 nmol/L;

• presence of multiple sexual partners or change of regular sexual partner;

• frequent vaginal intercourse (≥2–6 times per week);

• anal intercourse;

• history of childhood cutaneous warts;

• age >20 years;

• chronic smoking.

Children

The medicinal product may be used in children from 1 year of age.

Overdose

Cases of overdose have not been reported. Serious adverse events, apart from increased serum uric acid levels, are unlikely based on animal toxicity studies. Treatment is symptomatic and supportive.

Adverse reactions.

The only adverse effect that occurs most frequently during treatment with inosine pranobex in both adults and children is an increase in serum and urinary uric acid levels (usually remaining within normal limits), which typically returns to baseline values within a few days after completion of treatment.

Adverse reactions are categorized by frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); frequency unknown (cannot be estimated from available data).

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister, 2 or 4 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

LLC "DKP "Pharmaceutical Factory".

Manufacturer's location and address of business activity.

4, Korolova St., v. Stanishivka, Zhytomyr district, Zhytomyr region, 12430, Ukraine.