What are the Uses of Ganciclovir?
Ganciclovir is primarily used to treat and prevent cytomegalovirus (CMV) infections in immunocompromised individuals, such as those with HIV/AIDS (CD4 count <50 cells/mm³), organ transplant recipients, or chemotherapy patients. Key uses include:
CMV retinitis: Administered via intraocular implant (4.5 mg sustained release) or systemic therapy to prevent vision loss.
CMV colitis/pneumonia: Intravenous (IV) dosing (5 mg/kg every 12 hours for 14–21 days) for active infections.
Preemptive therapy: Oral valganciclovir (900 mg daily), a prodrug with 60% bioavailability, prevents CMV reactivation post-transplant.
How Does Ganciclovir Work ?
Ganciclovir works by selectively inhibiting viral DNA replication in cytomegalovirus (CMV) and related herpesviruses. As a synthetic guanosine analog, it undergoes a three-step phosphorylation process: first by the viral UL97 kinase (specific to CMV-infected cells), then by host kinases, forming ganciclovir triphosphate. This active form competes with natural dGTP, incorporating into viral DNA during replication.
Once integrated, ganciclovir’s lack of a 3′-hydroxyl group prevents DNA chain elongation, causing premature termination. Its triphosphate form has a prolonged intracellular half-life (~18–24 hours), sustaining antiviral activity with fewer doses.
You’ll see higher selectivity for CMV because UL97 kinase activation occurs predominantly in infected cells, minimizing harm to healthy ones. However, this mechanism still risks toxicity in dividing human cells (e.g., bone marrow), explaining side effects like neutropenia (~40% incidence).
What are the Side Effects of Ganciclovir?
Ganciclovir commonly causes bone marrow suppression and gastrointestinal issues. Key side effects include:
Neutropenia (low white blood cells) in ~40% of patients, raising infection risk.
Thrombocytopenia (low platelets) in ~20%, increasing bleeding tendency.
Anemia (low red blood cells) in ~19%.
Nausea/vomiting (20%) or diarrhea (15%).
Severe risks involve renal toxicity (10–15% incidence) requiring dose adjustments if creatinine clearance is <80 mL/min, and seizures (~5%), especially with IV use. You may also experience fever (10%) or elevated liver enzymes (8%).
Rarely, allergic reactions (rash, anaphylaxis) or central nervous system effects (confusion, headache) occur.
Who Shouldn’t Use Ganciclovir?
Ganciclovir is contraindicated in specific groups due to toxicity risks:
Hypersensitivity: You should avoid it if you’ve had allergic reactions (e.g., anaphylaxis) to ganciclovir, valganciclovir, or acyclovir (cross-reactivity risk <1%).
Pregnancy: Category C animal studies show fetal abnormalities. Use contraception during and for ≥90 days post-treatment.
Severe neutropenia (ANC <500 cells/μL) or thrombocytopenia (platelets <25,000/μL): Ganciclovir worsens bone marrow suppression (neutropenia occurs in ~40% of users).
Severe renal impairment (creatinine clearance <10 mL/min): Dose adjustments are insufficient; hemodialysis clears only ~50% of the drug.
What are the Available Tablets of Ganciclovir in Pakistan?
In Pakistan, Valcyte 450mg tablets are available, which contain the active ingredient ganciclovir in the form of valganciclovir. Valganciclovir is converted into ganciclovir in the body. These tablets are primarily used to treat or prevent cytomegalovirus (CMV) infections, particularly in patients with weakened immune systems, such as those with AIDS or organ transplant recipients.