Groviral 500

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT GROVIRAL 500 (GROVIRAL 500)

Composition:
Active substance: inosine pranobex;
1 tablet contains inosine pranobex 500 mg;
Excipients: maize starch, povidone K-25, magnesium stearate, mannite (E 421).

Pharmaceutical form. Tablets.

Main physical and chemical properties:
Round-shaped tablets, from almost white to yellowish-white, with a biconvex surface, with a slight specific odor.

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

Pharmacological properties.

Pharmacodynamics.
Groviral 500 is an antiviral agent with immunomodulatory properties. The medicinal product eliminates deficiency or dysfunction of cellular immunity by inducing maturation and differentiation of T-lymphocytes and T1-helper cells, enhancing the induction of lymphoproliferative response in mitogen- or antigen-activated cells.

Inosine pranobex modulates cytotoxicity of T-lymphocytes and natural killer cells, function of T8-suppressor and T4-helper cells, and increases the level of immunoglobulin G and complement surface markers.

Inosine pranobex increases synthesis of interleukin-1 (IL-1) and interleukin-2 (IL-2), regulates expression of IL-2 receptors. The drug significantly enhances secretion of endogenous gamma-interferon and reduces formation of interleukin-4 in the body.

The drug enhances the activity of neutrophilic granulocytes, chemotaxis and phagocytosis of monocytes and macrophages.

Inosine pranobex inhibits viral replication by incorporating inosine orotat acid into polyribosomes of virus-infected cells and by inhibiting adenylic acid attachment to viral mRNA.

Pharmacokinetics.
After oral administration 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 as metabolites.

Clinical characteristics.

Indications:

• Recurrent viral infections of the upper respiratory tract in patients with reduced immune status.
• Herpes labialis and facial herpes caused by herpes simplex virus (Herpes simplex).

Contraindications.
Hypersensitivity to the active substance or to any of the excipients of the medicinal product, acute gout, urolithiasis, severe renal insufficiency (Stage III), 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 excretion of uric acid, including diuretics, particularly thiazide diuretics (such as hydrochlorothiazide, chlorthalidone, indapamide) or loop diuretics (e.g., furosemide, torasemide, ethacrynic acid).

Groviral 500 may be used after, but not simultaneously with immunosuppressants, due to possible pharmacokinetic interference with desired therapeutic effects.

When used concomitantly with zidovudine (azidothymidine), formation of zidovudine nucleotide is enhanced via multiple mechanisms, including increased bioavailability of azidothymidine in plasma and increased intracellular phosphorylation in human blood monocytes. This results in enhanced effect of zidovudine.

Special precautions for use.
During treatment with inosine pranobex, transient increase in uric acid levels in blood serum and urine may occur, particularly in men and elderly patients; however, these values 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 catabolic metabolism of inosine in humans. This is not caused by drug-induced fundamental changes in enzyme function or renal clearance.

Therefore, the medicinal product should be used with particular caution in patients with gout, hyperuricemia, history of urolithiasis, or impaired renal function. During treatment, uric acid levels in these patients should be monitored.

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

With prolonged use of the medicinal product, there is a risk of kidney and gallbladder stone formation. During long-term treatment, serum and/or urine uric acid levels, liver function, blood count, and renal function should be regularly monitored in all patients.

Use during pregnancy or breastfeeding.

Pregnancy.
Studies on risk of fetal abnormalities and fertility impairment in humans have not been conducted. Groviral 500 should not be used during pregnancy except when the physician determines that potential benefit outweighs potential risk.

Breastfeeding.
It is unknown whether inosine pranobex passes into breast milk. Risk to infants 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.
Groviral 500 has no effect or negligible effect on the ability to drive or operate machinery.

Method of administration and dosage.
The medicinal product should be taken orally, preferably after meals and at regular intervals. If necessary, the tablet may be chewed, crushed, and/or dissolved in a small amount of water immediately before administration.

Duration of treatment is determined individually by the physician depending on the nosology, severity of the disease, and frequency of relapses; on average, treatment lasts 5–14 days. After disappearance of symptoms, the medicinal product should be continued for another 1–2 days.

Adults: recommended dose is 2 tablets of 500 mg, 3–4 times daily.

Children from 1 year of age: 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 body weight over 20 kg, administer adult dose).

For maximum treatment efficacy, it is best to start treatment at the onset of first symptoms or on the first day of illness.

Elderly patients.
The medicinal product can be used at standard adult doses — no dose adjustment is required.

Children.
The medicinal product is indicated for use in children from 1 year of age.

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

Adverse reactions.
The only adverse effect commonly observed during treatment with inosine pranobex in both adults and children is increased uric acid levels in blood serum and urine (usually remaining within normal limits), which typically return to baseline values within several days after completion of treatment.

Frequency of adverse reactions 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).

Reporting of adverse reactions following registration of the medicinal product is of significant importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of effectiveness of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life: 3 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, 4 blisters per carton.
Supply classification: Over-the-counter (without prescription).
Manufacturer: LLC "DKP "Pharmaceutical Factory".
Manufacturer's address and location of operations: Korolyova St., b. 4, Stanishivka village, Zhytomyr district, Zhytomyr region, 12430, Ukraine.
Marketing Authorization Holder: Limited Liability Company "Representation Baumann Pharm GmbH".
Address of the Marketing Authorization Holder: 66 Shyroka St., Lviv, 79052, Ukraine.