What are the potential adverse effects of ganciclovir, especially in immunocompromised individuals with pre-existing kidney or liver disease?

Adverse Effects of Ganciclovir

Myelosuppression—specifically neutropenia and thrombocytopenia—is the principal dose-limiting toxicity of ganciclovir, requiring dose reduction or treatment interruption in up to 40% of patients. 1

Primary Hematologic Toxicity

Bone marrow suppression is the most clinically significant adverse effect:

• Neutropenia (ANC <1000/µL) occurs in 29-41% of patients during maintenance therapy, with severe neutropenia (ANC <500/µL) developing in 3-6% 2
• Thrombocytopenia (platelets ≤50,000/µL) affects 5-6% of patients 2
• Approximately two-thirds of infants treated for congenital CMV develop substantial neutropenia during therapy 1, 3
• Anemia occurs in 19-25% of patients receiving IV ganciclovir 2

Critical monitoring requirements:

• Complete blood counts must be checked twice weekly during induction therapy and once weekly during maintenance 1, 3
• Severe neutropenia may necessitate granulocyte colony-stimulating factor (G-CSF) to ameliorate marrow suppression 1
• Dose reduction or complete interruption may be necessary when significant myelosuppression develops 1

Renal Toxicity

Ganciclovir causes nephrotoxicity that requires careful monitoring, particularly in patients with pre-existing renal impairment:

• Elevated serum creatinine (≥2.5 mg/dL) occurs in 16% of transplant recipients versus 10% on placebo 2
• The drug is substantially excreted by the kidney, and toxic reactions are more likely in patients with impaired renal function 2
• Renal function must be monitored regularly, as toxicity can occur and requires dose modification 1, 3
• Hemodialysis reduces plasma ganciclovir levels by approximately 50% 2

Risk Factors for Hematologic Toxicity

Specific patient characteristics increase the risk of severe adverse effects:

• Cancer chemotherapy increases thrombocytopenia risk 3.1-fold 4
• Creatinine clearance <20 mL/min increases thrombocytopenia risk 12.8-fold 4
• High-dose ganciclovir (≥12 mg/kg/day) increases thrombocytopenia risk 15.1-fold and leukopenia risk 7.8-fold 4
• Baseline white blood cell count <6000 cells/mm³ increases leukopenia risk 3.7-fold 4

Other Significant Adverse Effects

Gastrointestinal toxicity is common:

• Diarrhea affects 41-48% of patients 2
• Anorexia occurs in 15-19% 2
• Vomiting develops in 13-14% 2
• Potentially fatal gastrointestinal perforation and pancreatitis have been reported 2

Hepatic effects:

• Elevated liver enzymes (SGOT/SGPT) occur less frequently than bone marrow suppression but require monitoring 1, 2

Infusion-related complications:

• Thrombophlebitis at IV administration sites 1
• Each dose must be infused slowly over 1-2 hours to minimize toxicity 3

Neurologic effects:

• Neuropathy affects 8-21% of patients 2
• Seizures, confusion, and encephalopathy have been reported 2

Other systemic effects:

• Fever (35-48%), infection (8-13%), chills (7-10%), and sepsis (3-15%) 2
• Retinal detachment occurred in 8% of patients with CMV retinitis, though relationship to ganciclovir is unknown 2

Special Considerations in Immunocompromised Patients

Patients with HIV/AIDS and transplant recipients face additional risks:

• Common side effects of neutropenia and thrombocytopenia can overlap with manifestations of systemic CMV, adding complexity to management 5
• A multidisciplinary approach including infectious disease specialists is recommended for managing severe hematologic toxicity 5
• Most patients in transplant studies also received cyclosporine, which may contribute to renal impairment 2

Reproductive and Developmental Toxicity

Ganciclovir carries significant reproductive risks:

• The drug is Pregnancy Category C, with demonstrated embryotoxicity in rabbits and mice, and teratogenicity in rabbits 2
• Decreased fertility and hypospermatogenesis occurred in male mice and dogs at doses ranging from 0.2-10 mg/kg/day 2
• Mothers should discontinue nursing if receiving ganciclovir due to potential for serious adverse reactions in infants 2
• Use in pediatric patients warrants extreme caution due to probability of long-term carcinogenicity and reproductive toxicity 2

Alternative Therapy for Intolerance

When ganciclovir toxicity is unacceptable:

• Foscarnet may be considered as an alternative in patients who cannot tolerate ganciclovir due to severe bone marrow suppression 1
• However, foscarnet has significant nephrotoxicity (up to 30% of patients), requires saline fluid loading, and causes electrolyte disturbances in approximately one-third of patients 5, 6