Ganciclovir (Lyophilisate) Instructions for Use

ATC Code

J05AB06 (Ganciclovir)

Active Substance

Ganciclovir (Rec.INN WHO registered)

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleosides and nucleotides, excluding reverse transcriptase inhibitors

Pharmacological Action

Antiviral agent. It is a synthetic analog of guanine. Its chemical structure is close to acyclovir.

Inside the cell, Ganciclovir is sequentially metabolized into a monophosphate form with the participation of cellular deoxyguanosine kinase, and then into active Ganciclovir triphosphate. Acting as a substrate and being incorporated into DNA, Ganciclovir triphosphate competitively inhibits the synthesis of viral DNA. This leads to the suppression of DNA synthesis by inhibiting DNA chain elongation. Ganciclovir inhibits viral DNA polymerase more strongly than cellular polymerase.

It is active against cytomegalovirus, Herpes simplex virus type 1 and 2, Varicella zoster, and Epstein-Barr virus. Clinical studies have been conducted only for CMV infection.

Pharmacokinetics

After oral administration, it is poorly absorbed from the gastrointestinal tract. Bioavailability is 6-9%. C_max in blood plasma after oral administration is reached after 1.8 hours, after IV administration – within 1 hour. It is distributed in all tissues and crosses the placenta. V_d is 0.74 l/kg. Plasma protein binding is 1-2%. It is excreted in the urine. T_1/2 after oral administration is 3.1-5.5 hours, after IV administration – 2.9 hours.

After instillation of ganciclovir in the appropriate dosage form into the eye 5 times/day for 11-15 days for the treatment of superficial herpetic keratitis, plasma concentrations of ganciclovir were very low: on average 0.013 µg/ml (0=0.037).

Indications

Treatment and prevention of cytomegalovirus infection (including in AIDS, immunodeficiency associated with organ transplantation or chemotherapy), cytomegalovirus retinitis.

For use in ophthalmology: treatment of acute superficial keratitis caused by the herpes simplex virus.

ICD codes

Dosage Regimen

Lyophilisate

Individual. For oral administration – 1 g 3 times/day or 500 mg 6 times/day. For IV administration, the daily dose is 5-10 mg/kg. The frequency and duration of use depend on the treatment regimen.

Ganciclovir in the appropriate dosage form is instilled into the lower conjunctival sac of the affected eye 3-5 times/day for 7 days. The duration of treatment is no more than 21 days.

Adverse Reactions

From the hematopoietic system: neutropenia, thrombocytopenia, anemia, eosinophilia.

From the central nervous system: obsessive states or nightmares, ataxia, coma, confusion, insomnia, dizziness, headache, nervousness, paresthesia, psychoses, seizures.

From the digestive system: nausea, vomiting, dry mouth, abdominal pain, anorexia, diarrhea, flatulence, changes in laboratory parameters of liver function.

From the cardiovascular system: arrhythmia, arterial hypertension or hypotension.

Allergic reactions: fever, skin rash, itching, urticaria.

From the urinary system: hematuria, increased plasma creatinine and urea, increased blood urea nitrogen.

Local reactions: inflammation, pain, phlebitis at the injection site; from the organ of vision – blurred vision, eye irritation, punctate keratitis, conjunctival hyperemia.

Other: hypoglycemia, dyspnea, alopecia.

Contraindications

Neutropenia (absolute neutrophil count less than 0.5×10⁹/L), thrombocytopenia (platelet count less than 25×10⁹/L), severe renal impairment, congenital and neonatal cytomegalovirus infection, pregnancy, children under 12 years of age (for use in ophthalmology); hypersensitivity to ganciclovir or acyclovir.

Use in Pregnancy and Lactation

Ganciclovir is contraindicated during pregnancy. If it is necessary to use during lactation, the issue of stopping breastfeeding should be decided.

When used in high doses, suppression of fertility in women is possible. Women of childbearing age should use reliable methods of contraception during treatment.

Use in Renal Impairment

Contraindicated in severe renal impairment. Use with caution in patients with impaired renal function. Regular monitoring of renal function is necessary during treatment.

Pediatric Use

In children under 12 years of age, Ganciclovir is used in cases where the expected benefit of therapy outweighs the risk of side effects.

Special Precautions

Use with caution in patients with impaired renal function. This category of patients requires dose adjustment depending on the CC value.

Regular monitoring of peripheral blood counts and renal function is necessary during treatment. Depending on the degree of neutropenia and thrombocytopenia, dose adjustment or temporary discontinuation of treatment until signs of bone marrow recovery appear is required.

Concomitant use of ganciclovir with drugs such as dapsone, pentamidine, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, trimethoprim/sulfonamide combinations is justified only if the intended benefit of therapy outweighs the potential risk.

Ganciclovir should be administered only intravenously, because IM or SC injections cause severe tissue irritation. IV drip infusion should be accompanied by adequate hydration.

In children under 12 years of age, Ganciclovir is used in cases where the expected benefit of therapy outweighs the risk of side effects.

When used in high doses, suppression of spermatogenesis in men and fertility in women is possible. Men and women of childbearing age should use reliable methods of contraception during treatment. Men are also advised to use barrier methods of contraception for 90 days after the end of treatment.

Ganciclovir for topical use in ophthalmology is not intended for the treatment of cytomegalovirus retinitis.

Drug Interactions

Probenecid and other drugs that inhibit renal tubular secretion or reabsorption may reduce the clearance of ganciclovir and increase its half-life.

Concomitant use of ganciclovir with dapsone, pentamidine, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, trimethoprim/sulfonamide combinations may lead to additive toxicity.

Concomitant use of zidovudine and ganciclovir increases the risk of neutropenia.

Generalized seizures have been reported with the concomitant use of ganciclovir and the combination of imipenem and cilastatin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.