Inopranol

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT INOPRANOL

Composition:

Active substance: inosine pranobex;

One tablet contains 500 mg of inosine pranobex;

Excipients: mannitol (E 421), wheat starch, povidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, biconvex tablets of white or almost white color, with a score line on one side.

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

Pharmacological properties.

Pharmacodynamics. Inopranol is an antiviral agent with immunomodulatory properties. The drug normalizes (to individual norm) deficiency or dysfunction of cellular immunity by inducing maturation and differentiation of T-lymphocytes and T1-helpers, enhancing induction of lymphoproliferative response in mitogen- or antigen-activated cells. Inopranol modulates cytotoxic activity of T-lymphocytes and natural killers, function of T8-suppressors and T4-helpers, and also increases the amount of immunoglobulin G and complement surface markers. Inopranol increases synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), regulates expression of IL-2 receptors. Inopranol significantly enhances secretion of endogenous gamma-interferon and reduces production of interleukin-4 in the body. Inopranol enhances the activity of neutrophilic granulocytes, chemotaxis and phagocytosis of monocytes and macrophages. Inopranol inhibits viral synthesis by incorporating inosine orotic acid into polyribosomes of virus-infected cells and inhibits attachment of adenylate acid to viral mRNA.

Pharmacokinetics. After oral administration of the drug at a dose of 1.5 g, maximum plasma concentration of inosine pranobex is reached within 1 hour and amounts to 600 μg/ml. In the body, inosine pranobex is metabolized in the liver forming 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 by the kidneys as metabolites.

Clinical characteristics.

Indications.

Inopranol is indicated for reduced or dysfunctional cell-mediated immunity and clinical symptoms associated with such conditions:

• viral respiratory infections, primary and secondary, and immunosuppressive 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 warts) — 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 of the vulva and vagina (subclinical) or cervix (as part of combination therapy);
• viral hepatitis (as part of combination therapy);
• severe or complicated measles;
• subacute sclerosing panencephalitis (as part of combination therapy).

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.

The medicinal product should be administered with caution when used concomitantly with xanthine oxidase inhibitors (e.g., allopurinol) or agents promoting uric acid excretion, including diuretics, particularly thiazide diuretics (such as hydrochlorothiazide, chlorthalidone, indapamide) and loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

Inosine pranobex should not be used during immunosuppressive therapy, since concomitant use of immunosuppressants may affect its expected therapeutic effect due to specific pharmacokinetic mechanisms (use is possible only after completion of immunosuppressive therapy).

When used concomitantly with zidovudine (azidothymidine), formation of azidothymidine nucleotide is increased through 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 Inopranol, a temporary increase in serum and urinary uric acid levels may occur, particularly in men and elderly patients; however, these values usually remain within normal limits (up to 8 mg/dL and 0.420 mmol/L, respectively).

The increase in uric acid levels results from the catabolic metabolism of the inosine component of the active substance into uric acid and is not due to changes in enzyme activity or renal clearance caused by drug administration.

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, monitoring of uric acid levels is necessary in these patients.

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

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

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

Inopranol contains wheat starch, which may contain gluten, but only in extremely small amounts; therefore, the medicinal product is considered safe for people with celiac disease (gluten-sensitive enteropathy). However, patients with wheat allergy (distinct from celiac disease) should not take this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. Studies on the risk of fetal abnormalities and effects on fertility in humans have not been conducted. Inopranol should not be used during pregnancy except when the physician decides that the potential benefit outweighs the potential risk.

Breastfeeding. It is unknown whether inosine pranobex is excreted in breast milk. Risk to the infant 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 showed no effect on fertility.

Ability to affect reaction speed when driving or operating machinery. Inopranol has no effect or a negligible effect on the ability to drive or operate machinery.

Administration and Dosage

The medicinal product is 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.

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, divided into 3–4 doses per 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 over 20 kg, administer the adult dose).

Treatment Duration

Acute diseases: For conditions with a short course, the treatment duration is 5 to 14 days. After reduction in symptom severity, 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 reduction in symptom severity, or longer, depending on the physician’s decision.

Recurrent diseases: At the initial stage of treatment, the same recommendations apply 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 conditions should be resumed and continued for 1–2 days after symptom resolution. The treatment course may be repeated several times if necessary, as recommended by the physician based on clinical assessment.

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

• asymptomatic conditions: take for 30 days followed by a 60-day break;
• conditions with moderately expressed symptoms: take for 60 days followed by a 30-day break;
• conditions with severe symptoms: take for 90 days followed by a 30-day break.

Such 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 a day (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 medicinal product 5 days per week for 2 consecutive weeks per month, or 5 days per week every other week.

Such treatment may be repeated several times if necessary.

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:

• duration of genital papillomavirus infection exceeding 2 years or history of 3 or more recurrences;

• 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 (longer than 2 years);

• erythrocyte folate levels ≤ 660 nmol/L;

• having multiple sexual partners or change of a regular sexual partner;

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

• anal intercourse;

• history of cutaneous warts in childhood;

• age > 20 years;

• chronic smoking.

Children. The medicinal product is administered to children from 1 year of age.

Overdose.

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

Adverse Reactions

The only adverse effect most commonly observed during treatment with Inopranol 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 several days after discontinuation of treatment.

The frequency of the adverse reactions listed below is defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); frequency not known (cannot be estimated from available data).

Immune system disorders. Frequency not known: angioneurotic edema, hypersensitivity, urticaria, anaphylactic reaction.

Psychiatric disorders. Uncommon: nervousness.

Nervous system disorders. Common: headache, vertigo; uncommon: somnolence, insomnia; frequency not known: dizziness.

Gastrointestinal disorders. Common: vomiting, nausea, epigastric discomfort; uncommon: diarrhea, constipation; frequency not known: upper abdominal pain.

Skin and subcutaneous tissue disorders. Common: rash, pruritus; frequency not known: erythema.

Musculoskeletal and connective tissue disorders. Common: arthralgia.

Renal and urinary disorders. Uncommon: polyuria.

General disorders. Common: fatigue, discomfort.

Investigations. Very common: increased levels of uric acid in blood and urine; common: increased levels of urea, transaminases, and alkaline phosphatase in blood.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. No special storage conditions required.

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

Prescription status. Prescription only.

Manufacturer. Public Joint-Stock Company "Scientific and Production Center "Borshchahivskiy Chemical and Pharmaceutical Plant".

Manufacturer's address and location of operations. 17 Myru Street, Kyiv, 03134, Ukraine.