Groprinosin®-richter

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

Composition:

Active substance: inosine pranobex;

250 mg of inosine pranobex in 5 ml of syrup;

Excipients: methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), sucrose, sodium hydroxide (E 524), citric acid monohydrate (E 330), purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear liquid with a sweet taste.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antiviral agents for systemic use. Direct-acting antiviral agents.
ATC code J05AX05.

Pharmacological properties.

Pharmacodynamics.

Gropinosin®-Richter 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-helper cells, and by potentiating the induction of lymphoproliferative response in mitogen- or antigen-activated cells. Gropinosin®-Richter 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®-Richter enhances synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), and regulates expression of IL-2 receptors. Gropinosin®-Richter significantly increases secretion of endogenous gamma-interferon and reduces production of interleukin-4 in the body. Gropinosin®-Richter enhances the activity of neutrophil granulocytes, chemotaxis and phagocytosis of monocytes and macrophages. Gropinosin®-Richter inhibits viral replication by incorporating inosine orotic acid into polyribosomes of virus-infected cells and by inhibiting adenylic acid attachment 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 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 by the kidneys in the form of metabolites.

Clinical characteristics.

Indications.

• Viral infections caused by herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, measles virus, mumps virus, including in patients with immunodeficiency states;
• viral respiratory infections;
• papillomavirus infections of the skin and mucous membranes: anogenital warts, papillomavirus infection of the vulva, vagina, and cervix (as part of combination therapy);
• acute viral encephalitis (as part of combination therapy);
• viral hepatitis (as part of combination therapy);
• 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) or loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

Gropinosin®-Richter can be used after, but not simultaneously with immunosuppressants, due to a possible pharmacokinetic effect on desired therapeutic outcomes.

When used concomitantly with azidothymidine (zidovudine), formation of azidothymidine nucleotide is increased via multiple mechanisms, including increased plasma bioavailability of azidothymidine and enhanced intracellular phosphorylation in human blood monocytes. This results in potentiation of zidovudine effects under the influence of Gropinosin®-Richter.

Special precautions for use.

During treatment with Groprinosin®-Richter, a transient increase in serum and urinary uric acid levels may occur, but these levels usually remain within the normal range (up to the upper limit of normal—8 mg/dL or 0.420 mmol/L, respectively), particularly in elderly patients of both sexes and in men. The increase in uric acid levels results from the catabolic metabolism of inosine in the body and is not due to changes in enzyme activity or renal clearance caused by drug administration. Therefore, Groprinosin®-Richter should be used with caution in patients with a history of gout, hyperuricemia, urolithiasis, or impaired renal function. Patients should carefully monitor their uric acid levels during treatment.

With prolonged use of the drug (more than 3 months), it is advisable to regularly monitor laboratory parameters of liver and kidney function (transaminases, creatinine), serum and urinary uric acid levels, and perform blood tests.

In some patients, acute hypersensitivity reactions (angioneurotic edema, anaphylaxis, anaphylactic shock, urticaria) may occur. In such cases, treatment with Groprinosin®-Richter should be discontinued.

With prolonged use of the drug, there is a risk of stone formation in the ureters.

Excipients of the medicinal product.

The medicinal product Groprinosin®-Richter, syrup, contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed-type).

The medicinal product Groprinosin®-Richter, syrup, contains sucrose. This medicinal product should not be administered to patients with rare hereditary disorders such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Each 1 mL of the medicinal product Groprinosin®-Richter, syrup, contains 650 mg of sucrose. This should be taken into account in patients with diabetes mellitus.

Sucrose may be harmful to teeth.

This medicinal product contains less than 1 mmol (23 mg) of sodium per 80 mL, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Controlled studies on fetal development and fertility disorders in humans are lacking. It is unknown whether inosine pranobex is excreted in human breast milk. The drug should not be used during pregnancy or breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

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

Dosage and Administration

The medication should be taken orally only.

The daily dose depends on body weight, course, and severity of the disease.

The daily dose should be divided evenly into several equal doses to be taken throughout the day.

Adults, including elderly patients: The recommended daily dose is 50 mg/kg body weight (1 ml/kg), usually 3 g/day (60 ml of syrup per day), taken in 3 or 4 divided doses (20 ml of syrup 3 times daily or 15 ml of syrup 4 times daily). The maximum daily dose for adults is 80 ml of syrup (4 g of inosine pranobex).

Children from 1 year of age: The recommended daily dose is 50 mg/kg body weight (1 ml/kg per day), divided evenly into 3–4 doses according to the table below:

*To measure the dose, a dosing device with a graduated scale, which is included in the package, should be used.

Duration of treatment.

Acute diseases. For diseases with a short course, the treatment duration is 5–14 days. After a reduction in the severity of symptoms, treatment should be continued for another 1–2 days or longer, depending on the course of the disease and the patient's condition.

Viral diseases with prolonged course. Treatment should be continued for 1–2 weeks after a reduction in the severity of symptoms or longer, depending on the course of the disease and the patient's condition.

Recurrent diseases. At the initial stage of treatment, follow the same recommendations as for acute diseases. During maintenance therapy, the dose may be reduced to 500–1000 mg/day. Upon the first signs of recurrence, the daily dose recommended for acute diseases should be resumed and continued for 1–2 days after symptom resolution. The treatment course may be repeated several times as necessary, depending on the patient's condition and upon physician's recommendation.

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

Asymptomatic diseases – take for 30 days with a 60-day break;

Mildly symptomatic diseases – take for 60 days with a 30-day break;

Severe symptomatic diseases – take for 90 days with a 30-day break.

The treatment course should be repeated as many times as needed, with continuous monitoring of the patient's condition and indications for therapy extension.

External genital warts (condyloma acuminata) or cervical canal papillomavirus infection: administer 3 g/day for 14–28 days as monotherapy or as an adjunct to local therapy or surgical treatment according to the following regimens:

− for treatment of low-risk patients (patients with normal immunity or low risk of recurrence), administer the drug for 14–28 days until maximum viral eradication is achieved, followed by a 2-month break. The treatment course may be repeated using the same dose, with continuous monitoring of the patient's condition and indications for therapy continuation;

− for treatment of high-risk patients * (patients with immunodeficiency or high risk of recurrence), administer the drug 5 days per week consecutively for 1–2 weeks per month for 3 months. The treatment course should be repeated, with continuous monitoring of the patient's condition and indications for therapy continuation.

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 of high risk 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);
• Long-term use of oral contraceptives (longer than 2 years);
• Erythrocyte folate levels ≤ 660 nmol/L;
• Multiple sexual partners or change of regular sexual partner;
• Frequent vaginal intercourse (≥ 2–6 times per week);
• Anal sex;
• History of childhood cutaneous warts;
• Age > 20 years;
• Chronic smoking.

Children.

Do not use Groprinosin®-Richter syrup in children under 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 consistently observed adverse reaction during inosine pranobex treatment in adults and children is a temporary increase in serum and urinary uric acid levels (usually remaining within normal limits), which return to baseline normal values within several days after completion of therapy.

The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000); frequency not known (cannot be estimated due to lack of 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 levels of urea, transaminases, alkaline phosphatase.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product 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, should report any 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.

Shelf life after first opening of the bottle – 6 months.

Storage conditions.

Store at a temperature not exceeding 25 °C. Do not cool, do not freeze!

Keep out of reach of children.

Packaging.

150 ml of syrup in a bottle; 1 bottle in a cardboard pack with a dosing device with a measuring scale from 0.5 ml to 5 ml.

Prescription status.

Prescription only.

Manufacturer.

Gedeon Richter Polska Sp. z o.o.

Manufacturer's address.

5 J. Poniatowski Street, Grodzisk Mazowiecki, 05-825, Poland.

Marketing Authorization Holder.

JSC "Gedeon Richter", Hungary.

Address of the Marketing Authorization Holder.

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