GROPRIM

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GROPRIM (GROPRIM)

Composition:

Active substance: inosine pranobex;

One tablet contains 500 mg of inosine pranobex;

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

Pharmaceutical form. Tablets.

Main physicochemical properties: oval-shaped, biconvex tablets of a color ranging from almost white to cream.

Pharmacotherapeutic group.

Antiviral agents for systemic use. Direct-acting antiviral agents.

ATC code J05A X05.

Pharmacological Properties

Pharmacodynamics

Gropirim is an antiviral agent with immunomodulatory properties. The drug normalizes (to individual norm) cellular immunity by inducing maturation and differentiation of T-lymphocytes and T1-helper cells, enhancing the induction of lymphoproliferative response in mitogen- or antigen-stimulated cells. Gropirim modulates cytotoxic activity of T-lymphocytes and natural killer cells, regulates functions of T8-suppressor and T4-helper cells, and also increases immunoglobulin G levels and complement surface markers. Gropirim enhances synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), and regulates expression of IL-2 receptors. Gropirim significantly increases secretion of endogenous gamma-interferon and reduces production of interleukin-4 in the body. It enhances the activity of neutrophilic granulocytes, chemotaxis, and phagocytic function of monocytes and macrophages. Gropirim inhibits viral replication by incorporating inosine orotat acid into polyribosomes of virus-infected cells and by suppressing 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 drug is excreted renally in the form of metabolites.

Clinical Characteristics.

Indications.

Groprinosin is indicated for the treatment of decreased or impaired cell-mediated immunity and clinical symptoms associated with the following 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 component of the medicinal product; acute gout; hyperuricemia.

Interaction with other medicinal products and other forms of interaction.

The drug 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).

Isoprinosine may be administered after, but not simultaneously with, immunosuppressants, as a pharmacokinetic effect on the desired therapeutic outcomes may occur.

Concomitant use with zidovudine (azidothymidine) increases the formation of the azidothymidine nucleotide 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 Groprin, 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 reason for increased uric acid levels is the catabolic metabolism of inosine in humans. This occurs not due to a fundamental drug-induced alteration in enzyme function or renal clearance.

Therefore, the drug should be used with special caution in patients with gout, hyperuricemia, a history of urolithiasis, and in patients with impaired renal function. During treatment, uric acid levels should be monitored in these patients.

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

With prolonged use of the drug, there is a risk of kidney and gallbladder stone formation.

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.

Groprin contains wheat starch, which may contain gluten, but in extremely small amounts; therefore, the drug is considered safe for people with celiac disease (gluten-sensitive enteropathy). Patients with wheat allergy (distinct from celiac disease) should not take this medication.

Groprin contains mannitol (E 421), which may have a laxative effect.

Use during pregnancy or breastfeeding.

Pregnancy. Studies on the risk of fetal abnormalities and effects on fertility in humans have not been conducted. Groprin should not be used during pregnancy except when a physician determines 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 drug 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 a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The drug is taken 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 in 3–4 divided doses throughout the day.

Children aged 1 year and older: The dose is 50 mg/kg body weight per day (1 tablet per 10 kg body weight for children weighing up to 20 kg; for children weighing more than 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, depending on the physician's decision.

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

Chronic diseases: The drug 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.

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 (condyloma 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 drug 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): administer the drug 5 days per week for 2 consecutive weeks each month, or 5 days per week every other week, over a 3-month period.

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 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);

• Long-term contraceptive use (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 intercourse;

• Negative history of skin warts in childhood;

• Age > 20 years;

• Chronic smoking.

Children.

The drug may be administered to children aged 1 year and older.

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: symptomatic and supportive therapy.

Adverse reactions.

The only adverse effect that most commonly occurs during treatment with Groprim 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.

Adverse reactions are categorized by frequency 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 – drowsiness, 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 levels of uric acid in blood and urine; common – increased levels of urea, transaminases, alkaline phosphatase in blood.

Shelf life.

5 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 "ASTRAFARM", Ukraine.

Manufacturer's address and location of business activity.

6, Kyivska St., Vyshneve, Kyiv-Sviatoshynskyi district, Kyiv region, 08132, Ukraine.