What are the potential side effects of Gancyclovir (antiviral medication) therapy?

Ganciclovir Side Effects

The most clinically significant side effect of ganciclovir is bone marrow suppression, particularly neutropenia and thrombocytopenia, which occurs in up to 40% of patients and represents the major dose-limiting toxicity requiring close hematologic monitoring. 1

Hematologic Toxicity (Primary Concern)

Neutropenia

• Neutropenia is the most common and serious adverse effect, occurring in 29-41% of patients during maintenance therapy 2
• Absolute neutrophil count <500 cells/µL is a contraindication to starting ganciclovir 2
• Granulocytopenia typically develops during the first or second week of treatment but can occur at any time 2
• In pediatric patients with congenital CMV, approximately two-thirds develop substantial neutropenia during therapy 1
• Recovery usually begins within 3-7 days of discontinuing the drug 2
• Severe cases may require granulocyte colony-stimulating factor (G-CSF) to ameliorate marrow suppression 1

Thrombocytopenia

• Occurs in 19-25% of patients during maintenance therapy 2
• Platelet count <25,000 cells/µL is a contraindication to initiating therapy 2
• Risk factors include cancer chemotherapy (OR 3.1), creatinine clearance <20 mL/min (OR 12.8), and high-dose ganciclovir ≥12 mg/kg/day (OR 15.1) 3

Anemia

• Develops in 19-25% of patients during maintenance therapy 2
• Contributes to the overall hematologic burden requiring dose modification 4

Renal Toxicity

• Elevated serum creatinine occurs in 16% of transplant recipients receiving ganciclovir versus 10% on placebo 2
• Renal dysfunction may require dose modification 1
• The mechanism of renal impairment is not fully understood, though ganciclovir is primarily excreted via glomerular filtration and active tubular secretion 3

Gastrointestinal Effects

• Diarrhea is extremely common, occurring in 41-48% of patients 2
• Nausea and vomiting occur in 13-14% of patients 2
• Anorexia develops in 15-19% of patients 2
• Potentially fatal complications include gastrointestinal perforation and pancreatitis 2

Neurologic Effects

• Neuropathy occurs in 8-21% of patients 2
• Other neurologic manifestations include headache, confusion, seizures, tremor, and somnolence 2
• CNS effects require monitoring throughout therapy 5

Reproductive Toxicity

• Animal data indicate ganciclovir causes inhibition of spermatogenesis and subsequent infertility, which may be reversible at lower doses but irreversible at higher doses 2
• Suppression of fertility in females may also occur 2
• Women of childbearing potential should use effective contraception during treatment 2
• Men should practice barrier contraception during and for at least 90 days following treatment 2

Other Significant Adverse Effects

• Fever occurs in 35-48% of patients 2
• Catheter-related complications (infection, sepsis) occur in 4-9% of IV recipients 2
• Thrombophlebitis at IV administration sites 1
• Elevated liver enzymes (SGOT, SGPT) 2
• Retinal detachment in 8% of patients with CMV retinitis, though relationship to ganciclovir is unknown 2

Critical Monitoring Requirements

Complete blood counts must be monitored twice weekly during induction therapy and once weekly during maintenance therapy to detect early hematologic toxicity 6, 1

• Serum electrolytes and renal function should be monitored twice weekly during induction and weekly thereafter 6
• Regular monitoring of serum creatinine is essential, particularly in patients receiving concomitant nephrotoxic agents like cyclosporine 2

Clinical Management Considerations

Dose Modification

• Up to 40% of patients require dose reduction or complete interruption due to hematologic toxicity 1
• Dose adjustments are necessary for renal dysfunction 1

Alternative Therapy

• Foscarnet may be used for ganciclovir-intolerant patients, though it carries significant nephrotoxicity risk 6
• For ganciclovir-resistant CMV, foscarnet or combination therapy should be considered 5

High-Risk Populations

• Patients with pre-existing cytopenias or history of cytopenic reactions to other drugs require extreme caution 2
• Those receiving cancer chemotherapy, with creatinine clearance <20 mL/min, or on high-dose regimens (≥12 mg/kg/day) face substantially elevated risk 3
• Ganciclovir administered before adequate hematological recovery post-transplant may cause severe myelosuppression or graft failure 7

Infusion Precautions

• Each dose must be infused slowly over 1-2 hours to minimize acute toxicity 5
• Never infuse faster than the recommended duration 5