What is the recommended intravenous ganciclovir dosing schedule for treating cytomegalovirus disease and for prophylaxis after solid‑organ transplantation in immunocompromised adults, including dose adjustments for impaired renal function and monitoring requirements?

Ganciclovir Administration for CMV Disease and Prophylaxis

For CMV disease in immunocompromised adults, administer intravenous ganciclovir 5 mg/kg every 12 hours for 14-21 days as induction therapy, followed by 5 mg/kg once daily as lifelong maintenance, with each dose infused slowly over 1-2 hours and mandatory dose adjustments based on creatinine clearance. 1

Induction Therapy Protocols

Standard CMV Disease (Retinitis, Disseminated Disease)

• Administer 5 mg/kg IV every 12 hours for 14-21 days as the evidence-based standard for HIV-infected and other immunocompromised adults 1
• Each dose must be infused over 1-2 hours minimum—never infuse faster, as this causes acute toxicity and potential neuromuscular blockade 2, 1, 3
• An in-line filter is required for all IV administrations 2

CMV Encephalitis (High Failure Risk)

• Use combination therapy from the start: ganciclovir 5 mg/kg IV every 12 hours PLUS foscarnet 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 3 weeks 1
• Monotherapy fails frequently in CNS disease—combination achieves improvement or stabilization in 74% of cases 1

Sight-Threatening CMV Retinitis

• For lesions adjacent to the optic nerve or fovea, initiate combination therapy: ganciclovir 5 mg/kg IV every 12 hours plus foscarnet 60 mg/kg IV every 8 hours for 14-21 days 1

Maintenance (Suppressive) Therapy

• Administer 5 mg/kg IV once daily, 5-7 days per week, for life after completing induction 1
• CMV disease is not cured with current antivirals—discontinuing maintenance leads to rapid progression 1
• Exception: May consider discontinuation only if sustained immune reconstitution achieved (CD4 >100-150 cells/µL for ≥3-6 months) with close monitoring 1

Oral Maintenance Alternative

• Valganciclovir 900 mg once daily is preferred over IV for long-term maintenance due to superior bioavailability 1
• Oral ganciclovir 1000 mg three times daily is an alternative but less commonly used due to poor bioavailability (only 7.2% absorbed) 1, 4

Solid Organ Transplant Prophylaxis

• All kidney transplant recipients (except donor/recipient both CMV-negative) should receive oral ganciclovir or valganciclovir prophylaxis for at least 3 months post-transplant and 6 weeks after T-cell-depleting antibody treatment 1
• For high-risk transplant recipients (donor positive/recipient negative), valganciclovir 900 mg daily is the standard prophylactic regimen 5

Renal Dose Adjustments (Critical)

The CDC provides specific dose adjustments based on creatinine clearance—failure to adjust causes toxicity or therapeutic failure: 2, 3

Induction Dosing by CrCl:

• CrCl 50-69 mL/min: 2.5 mg/kg IV every 24 hours 3
• CrCl 25-49 mL/min: 1.25 mg/kg IV every 24 hours 3
• CrCl 10-24 mL/min: 0.625 mg/kg IV every 24 hours 3
• CrCl <10 mL/min or hemodialysis: 0.625 mg/kg IV three times weekly, administered after each dialysis session 2, 3

Maintenance Dosing by CrCl:

• CrCl 50-69 mL/min: 2.5 mg/kg IV every 24 hours 2, 3
• CrCl 25-49 mL/min: 1.25 mg/kg IV every 24 hours 2, 3
• CrCl 10-24 mL/min: 0.625 mg/kg IV every 24 hours 2, 3
• CrCl <10 mL/min or hemodialysis: 0.625 mg/kg IV after each dialysis 2, 3

Oral Ganciclovir Dose Adjustments:

• CrCl 50-69 mL/min: 1,500 mg daily 2, 3
• CrCl 25-49 mL/min: 1,000 mg daily 2, 3
• CrCl 10-24 mL/min: 500 mg daily 2, 3
• CrCl <10 mL/min or hemodialysis: 500 mg three times weekly after dialysis 2, 3

Valganciclovir Dose Adjustments:

• CrCl 40-59 mL/min: 450 mg daily 2
• CrCl 25-39 mL/min: 450 mg every 48 hours 2
• CrCl 10-24 mL/min: 450 mg twice weekly 2
• CrCl <10 mL/min or dialysis: Not recommended 2

Mandatory Monitoring Requirements

Hematologic Monitoring (Most Critical)

• Monitor CBC and platelets twice weekly during induction and once weekly during maintenance 2, 1, 3
• Myelosuppression is the major dose-limiting toxicity, requiring dose reduction or interruption in up to 40% of patients 1, 3
• For severe neutropenia, consider granulocyte colony-stimulating factor (G-CSF) 1, 6, 3

Renal Function Monitoring

• Monitor serum creatinine regularly (at least weekly during induction) as renal toxicity requires further dose modification 2, 1, 3
• Maintain adequate hydration throughout therapy to decrease nephrotoxicity 2, 3
• Avoid concomitant nephrotoxic drugs 2, 3

CMV Viral Load Monitoring

• Weekly CMV monitoring by nucleic acid testing or pp65 antigenemia is recommended during treatment 1

Critical Administration Requirements

• Handle with extreme caution: Undiluted IV solution is highly alkaline (pH 11)—avoid skin and mucous membrane contact 2, 3
• Dilute appropriately before administration and use an in-line filter 2
• Maintain good hydration before and during infusion 2

Congenital CMV (Distinct Protocol)

• For symptomatic congenital CMV with CNS involvement: 6 mg/kg IV every 12 hours for 6 weeks (total daily dose 12 mg/kg/day) 1, 6
• Valganciclovir is preferred for outpatient management when oral administration is feasible 6
• Begin treatment as soon as congenital CMV is confirmed, ideally in the neonatal period—do not delay for subspecialty consultations 6
• Approximately two-thirds of neonates develop substantial neutropenia requiring G-CSF 1

Resistance and Treatment Failure

• Long-term ganciclovir therapy selects for resistant CMV strains (IC₅₀ >3 µg/mL in vitro) 1, 3
• For documented resistance or treatment failure, switch to combination therapy: ganciclovir 5 mg/kg IV every 12 hours PLUS foscarnet 60 mg/kg IV every 8 hours for 3 weeks 1, 3
• Consider foscarnet monotherapy as alternative for resistant infections 1, 3

Common Pitfalls to Avoid

• Never shorten induction below 14 days—this increases risk of early disease progression 1
• Never discontinue maintenance therapy in immunocompromised patients without documented immune reconstitution 1
• Never infuse faster than 1-2 hours—rapid infusion causes acute toxicity 2, 1, 3
• Do not underdose overweight patients (>80 kg)—use actual body weight for creatinine clearance calculations, as ideal body weight underestimates renal function and causes underexposure 7
• Do not assume adequate dosing without monitoring—patients with CrCl 10-50 mL/min often achieve subtherapeutic levels and benefit from increased doses 4