Principal Side Effect of Ganciclovir Therapy
The principal side effect of ganciclovir therapy is bone marrow suppression, specifically manifesting as neutropenia, anemia, and thrombocytopenia. 1
Mechanism and Severity of Bone Marrow Suppression
- Myelosuppression is the major dose-limiting toxicity of ganciclovir, requiring dose reduction or interruption in up to 40% of patients due to hematologic toxicity 1, 2
- Neutropenia (ANC < 500/μL) occurs in approximately 19% of patients receiving maintenance therapy for CMV retinitis 3
- Severe neutropenia may necessitate treatment with granulocyte colony-stimulating factor to ameliorate marrow suppression 1
- In a phase III trial of ganciclovir treatment for congenital CMV infection, approximately two-thirds of infants experienced substantial neutropenia during therapy 1
Clinical Implications of Bone Marrow Suppression
- Dose reduction or complete interruption of therapy might be necessary in patients experiencing significant myelosuppression 1
- Regular monitoring of complete blood counts is essential during ganciclovir therapy, with recommended frequency of twice weekly during induction therapy and once weekly during maintenance 1
- Severe bone marrow failure can occur particularly in patients with renal impairment receiving inappropriate dosing 4
- In transplant recipients, the incidence of leukopenia, thrombocytopenia, and anemia ranges from 5-50% of patients 5
Other Adverse Effects of Ganciclovir
While bone marrow suppression is the principal side effect, other notable adverse effects include:
- Renal toxicity, manifested as increased serum creatinine, which may require dose modification 1
- Central nervous system effects including seizures, confusion, and headache 1, 6
- Gastrointestinal dysfunction including diarrhea (41% of patients), nausea (30%), and vomiting (21%) 3
- Elevated liver enzymes, though these occur less frequently than bone marrow suppression 1
- Thrombophlebitis at the site of intravenous administration 1
Monitoring Recommendations
- Complete blood counts should be monitored twice weekly during induction therapy and once weekly during maintenance therapy 1, 2
- Renal function should be monitored regularly as renal toxicity can occur and may require dose adjustment 1, 2
- For patients receiving IV cidofovir (an alternative to ganciclovir), blood urea nitrogen, creatinine, and urinalysis should be performed before each infusion 1
Clinical Considerations
- Valganciclovir, a prodrug of ganciclovir, has similar adverse effect profiles with bone marrow suppression being the principal concern 2, 3
- Patients with renal impairment are at particularly high risk for severe bone marrow toxicity due to decreased drug clearance and should receive appropriately adjusted doses 4, 7
- In patients who cannot tolerate ganciclovir due to severe bone marrow suppression, foscarnet may be considered as an alternative, though it has significant nephrotoxicity 1
The answer to the question is (a) bone marrow suppression.