Ganciclovir

Approved Indications:

• Cytomegalovirus (CMV) Infections: Treatment and prevention of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS).
• CMV Disease: Treatment of CMV disease in immunocompromised patients, including transplant recipients (solid organ and bone marrow transplants).
• Prevention of CMV Infection: Prophylaxis of CMV disease in high-risk patients undergoing transplantation.

Off-label/Clinically Accepted Uses:

• Treatment of congenital CMV infection in neonates.
• Treatment of CMV pneumonitis and CMV colitis in immunocompromised hosts.
• Other herpesvirus infections (less commonly used; valganciclovir preferred).
• Occasionally used in CMV encephalitis and CMV gastroenteritis.

Adults:

• Treatment of CMV Retinitis:
  Induction: 5 mg/kg IV every 12 hours for 14–21 days.
  Maintenance: 5 mg/kg IV once daily or oral valganciclovir.
• Prevention in Transplant Patients:
  5 mg/kg IV once daily, adjusted for renal function, for 7–14 days or longer based on risk.

Pediatrics:

• Dosing similar to adults, based on body weight (5 mg/kg every 12 hours); adjusted by renal function.

Elderly:

• No specific dose adjustment, but monitor renal function closely.

Renal Impairment:

• Dose adjustment required based on creatinine clearance; prolong dosing interval or reduce dose accordingly.

Administration Route:

• Intravenous infusion over 1 hour.
• Oral ganciclovir available but less bioavailable; valganciclovir is preferred for oral therapy.

Duration:

• Varies depending on indication and clinical response; typically 2–3 weeks induction followed by maintenance.

Ganciclovir is a synthetic analogue of 2'-deoxyguanosine. It is phosphorylated intracellularly by viral kinases (especially CMV UL97 kinase) to ganciclovir monophosphate and then converted by cellular kinases to the active triphosphate form. Ganciclovir triphosphate competitively inhibits viral DNA polymerase, causing chain termination during viral DNA replication. This action inhibits viral DNA synthesis and thereby prevents viral replication, leading to the control of CMV infection.

• Absorption: Poor oral bioavailability (~6% for oral ganciclovir); improved with valganciclovir (prodrug).
• Distribution: Widely distributed; crosses placenta and penetrates body fluids, including cerebrospinal fluid (CSF).
• Metabolism: Minimal metabolism; prodrug valganciclovir is hydrolyzed to ganciclovir in intestinal wall and liver.
• Elimination: Primarily renal excretion of unchanged drug via glomerular filtration and tubular secretion.
• Half-life: Approximately 2.5 to 4 hours in patients with normal renal function; prolonged in renal impairment.

• Pregnancy: FDA Category C. Animal studies show embryotoxicity and teratogenicity at high doses. Use during pregnancy only if clearly needed and benefits outweigh risks.
• Lactation: Excreted in breast milk; potential for serious adverse effects in nursing infants. Breastfeeding not recommended during treatment.

• Primary Class: Antiviral Agent
• Subclass: Anticytomegalovirus, nucleoside analogue DNA polymerase inhibitor

• Known hypersensitivity to ganciclovir or valganciclovir.
• Severe neutropenia or thrombocytopenia without medical supervision.
• Moderate to severe renal impairment without appropriate dose adjustment.

• Bone Marrow Suppression: Severe neutropenia, anemia, and thrombocytopenia are common; monitor complete blood counts regularly.
• Renal Impairment: Dose adjustment necessary; monitor renal function.
• Reproductive Toxicity: May cause infertility, teratogenicity, and carcinogenicity in animal studies.
• Mutagenesis and Carcinogenesis: Potential risks observed in animals; caution advised.
• Seizures and CNS Toxicity: Reported in rare cases; monitor patients with CNS disorders.
• Hypersensitivity Reactions: Anaphylaxis and severe skin reactions reported.
• Infection Risk: Use cautiously in immunocompromised patients; monitor for secondary infections.

Common Adverse Effects:

• Hematologic: Neutropenia, anemia, thrombocytopenia
• Gastrointestinal: Nausea, vomiting, diarrhea
• CNS: Headache, confusion, tremors
• Fever, rash

Serious and Rare Side Effects:

• Bone marrow suppression leading to severe infections or bleeding
• Seizures and encephalopathy
• Hypersensitivity reactions including anaphylaxis and Stevens-Johnson syndrome
• Hepatotoxicity (rare)

Timing: Side effects often occur during induction phase or with higher doses; reversible upon dose reduction or discontinuation.

• Other Myelosuppressive Agents: Additive bone marrow toxicity (e.g., zidovudine, trimethoprim-sulfamethoxazole).
• Probenecid: May increase ganciclovir levels by decreasing renal clearance.
• Immunosuppressants: No direct pharmacokinetic interactions but increased risk of infections.
• Nephrotoxic Drugs: Additive renal toxicity; monitor renal function.
• No significant CYP450 enzyme involvement.

• Valganciclovir has largely replaced oral ganciclovir due to better bioavailability.
• Updated dosing recommendations emphasize renal function-based adjustments to reduce toxicity.
• Black box warning highlights risk of myelosuppression, carcinogenicity, and teratogenicity.
• Monitoring guidelines reinforce frequent CBC and renal function assessment during therapy.
• Newer antiviral agents and CMV resistance testing recommended in refractory cases.

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Do not freeze the solution.
• Keep vial tightly closed when not in use.
• Discard unused solution as per local guidelines.