Ganciclovir

Indications

Ganciclovir is used for: CMV retinitis, Pneumonitis, Cytomegaloviral infections

Adult Dose

Ophthalmic Herpes simplex keratitis Adult: As 0.15% gel: Apply 1 drop in the inferior conjunctival sac of the affected eye 5 times daily (approx 3 hrly while awake) until corneal healing occurs. Maintenance: 1 drop tid for 7 days after healing. Intravenous CMV Retinitis Initial: 5 mg/kg IV q12hr, over 1 hr x14-21d Maintenance 5 mg/kg IV qD OR 6 mg/kg IV qD for 5 d/week CMV Prevention in Transplant Recipients Induction: 10 mg/kg/d div q12hr IV x7-14 d Maintenance 5 mg/kg IV qD x100-120 d after transplant OR 6 mg/kg IV qD for 5 d/week x100-120 d after transplant CMV Prevention in HIV Infected 5-6 mg/kg 5-7x/week IV (recurrence)

Child Dose

Ophthalmic Herpes simplex keratitis <2 years: Safety and efficacy not established 2 years or older: Apply 1 drop in the inferior conjunctival sac of the affected eye 5 times daily (approx 3 hrly while awake) until corneal healing occurs. Maintenance: 1 drop tid for 7 days after healing.

Renal Dose

Renal Impairment (IV Induction) CrCl 50-69 mL/min: 2.5 mg/kg IV q12hr CrCl 25-49 mL/min: 2.5 mg/kg IV qD CrCl <25 mL/min: 1.25 mg/kg IV qD Renal impairment: Dialysis patients: 1.25 mg/kg for induction or 0.625 mg/kg for maintenance, to be given post dialysis on days when dialysis is performed. CrCl (ml/min) Dosage Recommendation 10-24 1.25 mg/kg/day for induction, then 0.625 mg/kg/day for maintenance. 25-49 2.5 mg/kg/day for induction, then 1.25 mg/kg/day for maintenance. 50-69 2.5 mg/kg 12 hrly for induction, then 2.5 mg/kg/day for maintenance.

Administration

Reconstitution: Add 10 mL of sterile water for inj to the vial labelled as containing 500 mg to provide a soln containing 50 mg/mL. Withdraw the appropriate dose of reconstituted soln from the vial and further dilute in 50-250 (usually 100) mL of a compatible IV infusion soln.

Contra Indications

Hypersensitivity; absolute neutrophil count <500 cells/mm3; platelet count <25,000/mm3; pregnancy, lactation. Not to be used as a bolus inj.

Precautions

Renal impairment; preexisting cytopenias or history of cytopenic reactions to drugs; child; contraceptive precautions to be followed during and at least 90 days thereafter; care in administering only into veins with good blood flow. Avoid contact with the skin and eyes. Maintain adequate hydration during infusion. Monitor WBC and platelet counts regularly during treatment. Eye examinations should be conducted at least once every 4-6 wk during treatment for CMV retinitis. Lactation: excretion in milk unknown; use with caution

Pregnancy-Lactation

Interactions

Increased risk of haematologic toxicity w/ zidovudine. May increase serum levels of didanosine. Increased serum concentration w/ probenecid and other drugs that inhibit renal tubular secretion and resorption. Use of IV ganciclovir w/ oral mycophenolate mofetil may result in increased plasma concentrations of both drugs due to competition for renal tubular secretion. Concomitant use w/ immunosuppressive agents (e.g. azathioprine, ciclosporin, corticosteroids) may result in excessive suppression of bone marrow or the immune system. Generalised seizure may occur when taken w/ imipenem and cilastatin. Concurrent use w/ drugs that inhibit replication of rapidly dividing cells (e.g. dapsone, pentamidine, pyrimethamine, flucytosine, cytotoxic antineoplastic agents, amphotericin B, co-trimoxazole, other nucleoside analogues) may result in additive toxicity.

Adverse Effects

Side effects of Ganciclovir : Opthalmic >10% Blurred vision (60%),Eye irritation (20%) 1-10% Punctate keratitis (5%),Conjunctival hyperemia (5%) Intravenous >10% Neutropenia w/ ANC <1000/cu.mm (25-50%),Thrombocytopenia (20%) 1-10% Abnl LFTs,Anemia,Confusion,Headache,Nausea/vomiting,Neuropathy,Paresthesia,Pruritus,Retinal detachment,Rash,Sepsis,Weakness

Mechanism of Action

Ganciclovir is a synthetic guanine nucleoside analogue with activity against cytomegalovirus (CMV). It competitively inhibits the binding of deoxyguanosine triphosphate to DNA polymerase, thus inhibiting viral DNA synthesis.