Gropivirin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GROPIVIRIN® (GROPIVIRIN)

Composition:

Active substance: inosine pranobex;

One tablet contains 500 mg of inosine pranobex;

Excipients: corn starch, mannitol (E 421), povidone (Kollidon 25), magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: tablets from almost white to yellowish-white, oval, biconvex, elongated in shape, with a score line on one side, with a slight specific odor.

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

ATC code J05A X05.

Pharmacological Properties.

Pharmacodynamics.

Groprinosin® is an antiviral agent with immunomodulatory properties. The drug normalizes (to individual norm) the 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. Groprinosin® modulates cytotoxic activity of T-lymphocytes and natural killer cells, regulates functions of T8-suppressors and T4-helper cells, and also increases immunoglobulin G levels and complement surface markers. Groprinosin® enhances synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), and regulates expression of IL-2 receptors. Groprinosin® significantly increases secretion of endogenous gamma-interferon and reduces production of interleukin-4 in the body. Groprinosin® enhances the activity of neutrophilic granulocytes, chemotaxis, and phagocytosis by monocytes and macrophages. Groprinosin® inhibits viral replication by incorporating inosinoric acid into polyribosomes 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 renally.

Clinical characteristics.

Indications.

Groprivirin® is indicated for the treatment of decreased or dysfunctional cell-mediated immunity and clinical symptoms associated with such diseases:

• 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 any component of the drug, acute gout, hyperuricemia.

Interaction with other medicinal products and other forms of interaction.

The drug should not be taken simultaneously with immunosuppressants. The drug should be administered with caution together with xanthine oxidase inhibitors (e.g., allopurinol) or medicinal products promoting uric acid excretion, including diuretic agents – thiazide diuretics (such as hydrochlorothiazide, chlorothalidone, indapamide) or loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

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

When used concomitantly with zidovudine (azidothymidine), increased formation of the azidothymidine nucleotide occurs as a result of increased bioavailability of azidothymidine in blood plasma and enhanced intracellular phosphorylation in human blood monocytes. This leads to potentiation of zidovudine's effect.

Special precautions for use

During treatment with Groprinosin®, a transient increase in serum and urinary uric acid levels may occur, particularly in elderly individuals and younger men. However, these levels 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 phenomenon does not result from a fundamental drug-induced alteration in enzyme function or renal clearance.

Therefore, the drug should be administered with particular caution in patients with a history of gout, hyperuricemia, urolithiasis, or impaired renal function. During treatment, monitoring of uric acid levels is recommended in these patients.

In some individuals, acute hypersensitivity reactions (angioneurotic edema, anaphylactic shock, urticaria) may occur. In such cases, therapy with Groprinosin® should be discontinued immediately.

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

During long-term treatment, regular monitoring of serum and/or urinary uric acid levels, liver function, blood count, and renal function is recommended 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® should not be used during pregnancy unless, in the physician’s judgment, the potential benefit outweighs the potential risk to the fetus.

Breastfeeding. It is unknown whether inosine pranobex is excreted in human 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 affect reaction speed when driving or operating machinery

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

However, patients should be advised that the drug may cause dizziness or other nervous system-related adverse reactions.

Dosage and Administration

The medication should be 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 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, divided evenly 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 weighing up to 20 kg; for children weighing more than 20 kg, administer the adult dose).

Duration of treatment.

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

Viral diseases with prolonged course: Treatment should continue for 1–2 weeks after symptoms subside, or longer, as determined by the physician.

Recurrent diseases: Initial treatment follows 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. The treatment course 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 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.

Dosage in special indications

External genital warts (condylomata acuminata) or cervical canal papillomavirus infection: Take 2 tablets three times daily (3 g) either 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 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 5 days per week for 2 consecutive weeks per month, or 5 days per week every other week for 3 months.

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.

* 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);

• 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 medication 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 is symptomatic and supportive.

Side effects.

The only side effect commonly observed during treatment with Groprivirin® in both adults and children is an increase in serum and urinary uric acid levels (usually remaining within normal limits and typically returning to baseline values within a few days after completion of therapy).

Immune system disorders: angioneurotic edema, hypersensitivity, urticaria, anaphylactic reaction.

Psychiatric disorders: nervousness.

Nervous system disorders: headache, vertigo, somnolence, insomnia, dizziness.

Gastrointestinal disorders: vomiting, nausea, epigastric discomfort, diarrhea, constipation, abdominal pain (in the upper abdomen).

Skin and subcutaneous tissue disorders: rash, pruritus, erythema.

Musculoskeletal and connective tissue disorders: arthralgia.

Renal and urinary disorders: polyuria.

General disorders and administration site conditions: fatigue, malaise.

Investigations: increased levels of uric acid in blood and urine.

Elevated levels of urea, transaminases, and alkaline phosphatase in blood.

Shelf life. 2 years.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 tablets in a blister. 2 or 5 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.