Groprinosin® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GROPRINOSIN® FORTE (GROPRINOSIN® FORTE)

Composition:

Active substance: inosine pranobex;

1 tablet contains 1000 mg of inosine pranobex;

Excipients: potato starch, povidone K-25, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: oval, biconvex tablets from white to almost white in color, 20 mm in length, 10 mm in width, with a break line on one side and engraving "F" on the other side.

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

Pharmacological properties.

Pharmacodynamics.

Gropinosin® Forte is an antiviral agent with immunomodulatory properties. The drug normalizes (to individual norm) the condition in case of deficiency or dysfunction of cellular immunity by inducing maturation and differentiation of T-lymphocytes and T1-helper cells, and by enhancing the induction of lymphoproliferative response in mitogen- or antigen-activated cells. Gropinosin® Forte modulates cytotoxic activity of T-lymphocytes and natural killer cells, function of T8-suppressor and T4-helper cells, and also increases immunoglobulin G levels and complement surface markers. Gropinosin® Forte increases synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), and regulates expression of IL-2 receptors. Gropinosin® Forte significantly enhances secretion of endogenous gamma-interferon and reduces production of interleukin-4 in the body. Gropinosin® Forte enhances the activity of neutrophilic granulocytes, chemotaxis and phagocytosis by monocytes and macrophages. Gropinosin® Forte inhibits viral replication by incorporating inosine pranobex into polysomes of virus-infected cells and by inhibiting the attachment of adenylic 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 mcg/mL. In the body, 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 metabolites are excreted by the kidneys.

Clinical characteristics.

Indications.

Gropinazin® Forte 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 inside 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 types of interactions.

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) or loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

Gropinazin® Forte may be used after, but not simultaneously with immunosuppressants, due to the potential pharmacokinetic impact on desired therapeutic effects.

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

Special precautions for use

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

Therefore, Groprinosin® Forte 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, treatment with Groprinosin® Forte must be discontinued immediately.

Prolonged use of the drug may increase the risk of kidney and gallbladder stone formation.

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

Use during pregnancy or breastfeeding

Pregnancy. Studies on the risk of fetal abnormalities or effects on fertility in humans have not been conducted. Groprinosin® Forte should not be used during pregnancy except when, in the opinion of the physician, the expected benefit outweighs the potential risk.

Breastfeeding. It is unknown whether inosine pranobex is excreted in human breast milk. The drug should not be used during breastfeeding, except when, in the opinion of the physician, the expected benefit outweighs the potential risk.

Fertility. There are no data on the effect of the drug on human fertility. Animal studies have shown no adverse effects on fertility.

Ability to affect reaction speed when driving or operating machinery

Groprinosin® Forte has no effect or only a negligible effect on the ability to drive or operate machinery.

Dosage and Administration

The medicinal product is administered orally. The daily dose depends on body weight and the severity of the disease; the dose should be evenly divided into doses taken 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 (half a tablet per 10 kg body weight), usually 3 g/day (3 tablets), with a maximum dose of 4 g/day (4 tablets); administer orally, divided evenly into 3–4 doses per day.

Children from 1 year of age: The dose is 50 mg/kg body weight per day (half a 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 ranges from 5 to 14 days. After symptom severity decreases, treatment should be continued for an additional 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, depending on the physician's decision.

Recurrent diseases: At the initial stage, the same recommendations as for acute diseases apply. During maintenance therapy, the dose may be reduced to 500–1000 mg (half a tablet – 1 tablet) 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, as recommended by the physician based on clinical assessment.

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

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

Dosing for Special Indications

External genital warts (anogenital condylomata acuminata) or cervical canal papillomavirus infection: 1 tablet 3 times daily (3 g) is prescribed 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): the medicinal product is administered continuously for 14–28 days within a 3-month period, followed by a 2-month treatment break; then therapy is continued until lesions decrease or disappear;
• high-risk patients * (patients with immunodeficiency or high risk of recurrence): within a 3-month period, the drug is administered 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 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.

* Factors indicating high risk of 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 (longer 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 cutaneous warts in childhood;
• age > 20 years;
• chronic smoking.

Children

The medicinal product may be 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 studies. Treatment is symptomatic and supportive.

Adverse Reactions

The only adverse effect most commonly observed during treatment with Groprinosin® Forte 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 completion of treatment.

Adverse reactions are categorized by frequency as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 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, malaise.

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

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life.

2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 1 or 3 blisters per cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

Gedeon Richter Poland Sp. z o.o.

Manufacturer's address.

5, ul. Księcia J. Poniatowskiego, Grodzisk Mazowiecki, 05-825, Poland.

Marketing Authorization Holder.

JSC "Gedeon Richter", Hungary.

Address of Marketing Authorization Holder.

H-1103 Budapest, 19-21, Demrédi út, Hungary.