What is the recommended dose of ganciclovir (antiviral medication) for the treatment of cytomegalovirus (CMV) infections?

Ganciclovir Dosing for CMV Infections

For treatment of CMV disease, administer intravenous ganciclovir 5 mg/kg every 12 hours for 2-3 weeks (induction), followed by maintenance therapy at 5 mg/kg once daily or oral valganciclovir 900 mg daily. 1, 2

Induction Therapy Dosing

Standard induction treatment requires IV ganciclovir 5 mg/kg every 12 hours for 14-21 days. 1, 3 This dosing applies to:

• CMV retinitis: 5 mg/kg IV every 12 hours for 14-21 days 1, 3
• CMV encephalitis: 5 mg/kg IV every 12 hours for 2-3 weeks, though monotherapy often fails 1, 2
• CMV gastrointestinal disease: 5 mg/kg IV every 12 hours for 14 days 4
• Pediatric transplant recipients: All CMV disease requires IV ganciclovir treatment 2

Combination Therapy for Severe CNS Disease

For CMV encephalitis or myelitis, particularly in HIV-infected patients, combination therapy with ganciclovir (5 mg/kg IV every 12 hours) plus foscarnet (60 mg/kg IV every 8 hours OR 90 mg/kg IV every 12 hours) for 3 weeks achieves improvement or stabilization in 74% of patients. 1, 2 This combination is superior to monotherapy because effective CNS concentrations are difficult to achieve with either agent alone. 1

Maintenance Therapy Dosing

Following successful induction, maintenance options include:

• Oral valganciclovir 900 mg once daily (preferred for adults) 1
• IV ganciclovir 5 mg/kg once daily 1, 3
• Oral ganciclovir 1000 mg three times daily with food (alternative, though valganciclovir preferred) 3

Prophylaxis Dosing

For CMV prophylaxis in transplant recipients, use oral ganciclovir 1000 mg three times daily with food or oral valganciclovir. 3 The KDIGO guidelines recommend all kidney transplant recipients (except donor/recipient both CMV-negative) receive prophylaxis for at least 3 months post-transplant. 2

Renal Dose Adjustments

Dosing must be adjusted for renal impairment based on creatinine clearance: 3

• CrCl ≥70 mL/min: Standard dosing (1000 mg TID or 500 mg every 3 hours, 6x/day)
• CrCl 50-69 mL/min: 1500 mg once daily or 500 mg TID
• CrCl 25-49 mL/min: 1000 mg once daily or 500 mg BID
• CrCl 10-24 mL/min: 500 mg once daily
• CrCl <10 mL/min: 500 mg three times per week following hemodialysis

Critical caveat: Undialyzed patients with serum creatinine >3.0 mg/dL may achieve excessive trough levels (3-8 mcg/mL) despite dose adjustments, and may require further dose reduction to 1.25 mg/kg/day. 5

Pediatric Dosing Considerations

Pediatric renal transplant recipients receive 5 mg/kg IV every 12 hours for induction. 6 For oral therapy, children require higher doses than adults (approximately 46.7 mg/kg every 12 hours or up to 50 mg/kg every 12 hours) due to lower bioavailability and greater clearance. 6

For congenital CMV infection, begin valganciclovir as soon as diagnosis is confirmed, ideally in the neonatal period, for a 6-month course. 7 Alternative IV ganciclovir dosing is 6 mg/kg every 12 hours if oral administration is not feasible. 7

Monitoring Requirements

Complete blood counts and platelet counts should be monitored twice weekly during induction therapy and once weekly during maintenance therapy. 8 Serum creatinine or creatinine clearance must be followed carefully to allow dosage adjustments. 3

Weekly CMV monitoring by nucleic acid testing or pp65 antigenemia is recommended during treatment. 2

Critical Toxicity Management

Myelosuppression is the major dose-limiting toxicity, requiring dose reduction or interruption in up to 40% of patients. 1, 8

• Do not administer ganciclovir if absolute neutrophil count <500/µL or platelets <25,000/µL 3
• Granulocyte colony-stimulating factor can be used for severe neutropenia 1, 2, 8
• Renal toxicity may occur, manifesting as increased serum creatinine requiring dose modification 1, 8

High-Risk Populations Requiring Intensified Therapy

Patients at highest risk for treatment failure or relapse include: 5

• Donor CMV-positive/recipient CMV-negative serostatus (primary infection risk)
• Liver transplant recipients
• Patients receiving anti-rejection therapy or polyclonal anti-thymocyte globulin
• Renal transplant recipients with six-antigen MHC mismatches

These patients may require longer induction courses, combination therapy, or extended maintenance regimens. 5

Common Pitfalls to Avoid

• Never use oral ganciclovir for induction therapy - bioavailability is only 4.9% in pediatric patients and insufficient for acute treatment 3, 6
• Do not delay treatment while awaiting subspecialty consultations - early initiation provides optimal benefit 7
• Relapse occurs in approximately 50% of patients after stopping therapy - maintenance therapy is essential for most patients 4, 9
• Resistance can develop with inadequate dosing - one patient receiving erroneously low oral doses developed GCV resistance requiring foscarnet 6