Virgan

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

Composition:

Active substance: ganciclovir;

1 g of gel contains ganciclovir 1.5 mg;

Excipients: benzalkonium chloride, carbomer, sorbitol (E 420), sodium hydroxide, purified water.

Pharmaceutical form. Eye gel.

Main physicochemical characteristics: colorless gel.

Pharmacotherapeutic group. Ophthalmological agents. Antiviral agents. Ganciclovir. ATC code S01AD09.

Pharmacological Properties.

Pharmacodynamics.

Ganciclovir, 9-[(1,3-dihydroxy-2-propoxy)]guanine, or DHPG, is a nucleoside that inhibits in vitro replication of human Herpes viruses (Herpes simplex types 1 and 2, cytomegalovirus) and adenoviruses of serotypes 1, 2, 4, 6, 8, 10, 19, 22, 28.

In infected cells, ganciclovir is converted into ganciclovir triphosphate, the active form of the active substance.

Phosphorylation occurs predominantly in infected cells, with ganciclovir triphosphate concentrations being 10 times lower in non-infected cells.

The antiviral activity of ganciclovir triphosphate consists of inhibition of viral DNA synthesis via two mechanisms: competitive inhibition of viral DNA polymerases and direct incorporation into viral DNA, thereby blocking its elongation.

Pharmacokinetics.

In humans, after instillation of the drug into the eyes five times daily for 11–15 days for the treatment of superficial herpetic keratitis, plasma levels, measured using a sensitive analytical method (quantification limit – 0.005 mcg/mL), were very low: on average 0.013 mcg/mL (range: 0–0.037 mcg/mL).

Ophthalmic pharmacokinetic studies in rabbits confirmed rapid and significant penetration of ganciclovir into the cornea and anterior segment of the eye, with concentrations exceeding the mean effective dose (ED50) maintained for several hours.

Clinical characteristics.

Indications.

Treatment of acute superficial keratitis caused by herpes simplex virus.

Contraindications.

Hypersensitivity to ganciclovir, acyclovir, or to any component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

If used with any other ophthalmic medicinal products, an interval of at least 15 minutes is recommended between the application of two medicinal products. VIRA**®** should be administered last.

Although the amount of ganciclovir reaching the systemic circulation after ocular administration is negligible, the risk of drug interactions cannot be completely excluded.

The following interactions have been observed with systemic administration of ganciclovir.

Ganciclovir plasma protein binding is approximately 1–2 %; therefore, interactions involving displacement from binding sites are unlikely.

Concomitant administration of drugs that suppress replication in rapidly dividing cell populations, such as bone marrow, spermatogonial cells, germinal skin layers, and gastrointestinal mucosa, may result in combined additive toxicity when administered simultaneously, before, or after ganciclovir. Due to the potential for additive toxicity, concomitant use of ganciclovir with dapsone, pentamidine, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, trimethoprim/sulfonamide combinations, or other nucleoside analogues should only be considered if the potential benefit outweighs the risks.

Since zidovudine, like ganciclovir, may cause neutropenia, concomitant use of these agents during induction therapy with ganciclovir is not recommended. Studies have shown that simultaneous administration of maintenance doses of ganciclovir and zidovudine at recommended doses results in severe neutropenia in most patients.

In patients who received ganciclovir and imipenem-cilastatin simultaneously, cases of generalized seizures have been observed.

Probenecid, as well as other drugs that inhibit renal tubular secretion or reabsorption, may potentially reduce the renal clearance of ganciclovir and prolong its plasma half-life.

Special precautions for use

This medicinal product is not intended for the treatment of cytomegalovirus (CMV) retinitis.

Efficacy against keratoconjunctivitis caused by other types of viruses has not been established.

No specific clinical studies have been conducted in patients with immunodeficient conditions.

The medicinal product contains 2.625 μg of benzalkonium chloride per drop of gel, equivalent to 0.075 mg/g.

Benzalkonium chloride may be absorbed by soft contact lenses and may cause discoloration of contact lenses. Contact lenses must be removed before application of the product and should not be reinserted earlier than 15 minutes after instillation.

Benzalkonium chloride may also cause eye irritation, particularly in cases of dry eye or corneal pathology. Patients should be informed of the need to consult a physician if they experience unusual sensations, burning, or eye pain after using the product.

Use during pregnancy and breastfeeding

There is insufficient experience regarding the use of VIRA**GAN® during pregnancy or breastfeeding to assess safety during these periods.

In animal studies, teratogenic effects and effects on fertility (reproductive capacity) were observed following oral or intravenous administration of ganciclovir. In addition, ganciclovir demonstrated potential genotoxicity with a low safety profile.

Therefore, the use of this medicinal product during pregnancy or breastfeeding is not recommended, except in the absence of alternative treatment options.

Women of childbearing potential must use contraception during treatment with VIRA**GAN® and for six months after discontinuation of treatment.

Due to the genotoxicity observed in animal studies, men using VIRA**GAN® are advised to use contraceptive methods (condoms) during treatment and for three months after its completion.

Ability to influence reaction speed while driving or operating machinery

Patients should refrain from driving vehicles or operating machinery if any visual disturbances occur during treatment.

Administration and Dosage

The medication is instilled into the lower conjunctival sac of the affected eye.

One drop 5 times a day until complete corneal re-epithelialization, then one drop 3 times a day for 7 days. The duration of treatment usually does not exceed 21 days.

Children

The use of the medicinal product in children under 18 years of age is not recommended, as specific studies have not been conducted.

Overdose.

Not observed.

Side effects

Eye disorders

Very common:

Transient burning or stinging sensation, eye irritation, blurred vision.

Common:

Superficial punctate keratitis, conjunctival hyperemia.

Allergic reactions, visual disturbances, eye irritation have been reported.

Reporting of suspected side effects

Reporting of suspected side effects after authorization of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy of the medicinal product through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life: 3 years.

Shelf life after opening the tube: 4 weeks.

Storage conditions: Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging: 5 g in a tube with a screw-cap nozzle, 1 tube per cardboard box.

Prescription status: Prescription only.

Manufacturer:

Farmila - Thea Farmaceutici S.p.A. /
Farmila - Thea Farmaceutici S.r.L.

Manufacturer's address:

Via Enrico Fermi 50, Settimo Milanese, 20019, Italy.

Marketing Authorization Holder:

Laboratoires Thea

Pharmacovigilance contact person in Ukraine: [email protected] or by phone (044) 467-57-70 (24/7).

Address of the Marketing Authorization Holder and/or its representative:

12 rue Louis Bleriot, 63100 Clermont-Ferrand Cedex 2, France.